Understanding Mitochondrial Dysfunction in Long COVID

Last reviewed: October 2026

AI Answer

Long COVID mitochondrial dysfunction is an area of growing research, particularly in relation to fatigue, post-exertional malaise (PEM) and reduced exercise capacity. Studies have found abnormalities in how muscles and cells produce and use energy, including changes in mitochondrial function and energy metabolism.

However, mitochondrial dysfunction is unlikely to explain Long COVID on its own. Immune, autonomic, vascular and metabolic changes may interact, and researchers are still working out how these processes connect.

Key Points

• Mitochondria produce much of the energy cells need in the form of ATP.
• Research has found changes in energy metabolism and mitochondrial function in some people with Long COVID.
• These changes may help explain why ordinary physical or cognitive activity can require far more energy than it did before illness.
• Studies of PEM have found metabolic and muscle abnormalities after exertion, but the mechanisms behind PEM are likely to involve more than mitochondria alone.
• Mitochondrial dysfunction is one possible part of Long COVID biology, not a proven single cause of the condition.

Mitochondria and Long COVID: Why Your Cells Might Be Running on Empty

If you’ve ever been told to “push through” fatigue, it may seem strange to discover that researchers are looking much deeper than motivation, fitness or willpower.

They are looking inside our cells.

Mitochondria are tiny structures found in most cells in the body. They help produce the energy that keeps you thinking, moving and breathing. You can think of them as microscopic power plants — although in Long COVID, researchers are investigating whether parts of that energy system are working differently.

For someone living with the condition, that question is not particularly abstract.

Why can a shower feel like exercise? Why can concentrating on a conversation leave you exhausted? Why can you manage something today and feel significantly worse tomorrow?

Changes in the way the body produces and uses energy may be one piece of that puzzle.

What Are Mitochondria, and Why Do They Matter?

Mitochondria are often described as the body’s energy factories because one of their main jobs is producing ATP (adenosine triphosphate), the molecule cells use as a readily available source of energy.

But mitochondria do much more than keep the lights on. They are also involved in metabolism, oxidative stress, immune signalling and programmed cell death.

That means problems involving mitochondrial function could potentially have effects beyond simply feeling tired.

Imagine a city whose power network becomes less efficient. The lights may still work, but activities that once required little thought suddenly consume a much larger share of the available resources.

That is only an analogy  Long COVID is not simply a case of mitochondria “running out of power.” But it helps explain why researchers are interested in what happens to cellular energy metabolism after COVID.

What Has Research Actually Found?

Researchers have found evidence that energy metabolism can be altered in some people with Long COVID, but the picture is more complicated than simply saying that mitochondria stop working.

One particularly interesting area is what happens after exertion.

A 2024 study compared 25 people with Long COVID with 21 healthy participants before and after a maximal cycling test. The exercise triggered post-exertional malaise in the Long COVID group.

When researchers examined muscle tissue, they found differences including altered energy metabolism, muscle damage and reduced mitochondrial function after exercise.

That matters because PEM is not simply feeling tired after doing too much. Symptoms can worsen hours later and may affect far more than energy levels.

The study was small, so it cannot tell us that mitochondrial dysfunction causes PEM or that the same abnormalities occur in everyone with Long COVID.

But it provides something important: biological evidence that the body’s response to exertion can be different in Long COVID.

→ Read more: Post-Exertional Malaise: Why Symptoms Worsen After Activity

Why Might Energy Production Be Different?

Researchers are investigating several possibilities.

SARS-CoV-2 infection can affect cellular metabolism and increase oxidative stress. Persistent immune activation and inflammation may also influence how cells produce and use energy after the acute infection has passed.

At the same time, energy production does not happen in isolation.

Blood flow helps deliver oxygen and nutrients to tissues. The autonomic nervous system helps regulate circulation and the body’s response to activity. The immune system communicates constantly with metabolic pathways.

So if several of these systems are disrupted at the same time, the result may be more complicated than one faulty cellular “battery”.

Mitochondrial changes may therefore be one part of a wider biological problem rather than a standalone explanation for Long COVID.

→ Read more: What Causes Long COVID? What Researchers Know So Far

The Immune–Mitochondrial Connection

The immune system and mitochondria are closely connected.

Immune cells need energy to function, while mitochondria themselves participate in immune signalling and the cellular response to stress. Inflammation and oxidative stress can also affect mitochondrial function.

This has led researchers to investigate whether immune dysregulation and altered energy metabolism may reinforce one another in some people with Long COVID.

But we do not yet know whether mitochondrial changes begin early in the illness, develop because of persistent immune or vascular problems, or represent a mixture of several processes.

That distinction is important.

Finding altered mitochondrial function tells us something may be happening at the cellular level. It does not automatically tell us what started the problem — or whether directly targeting mitochondria will make someone better.

→ Read more: Long COVID and the Immune SystemWhat Might This Feel Like in Real Life?

Mitochondria are microscopic. The problem they may be contributing to does not feel microscopic at all.

It can feel like waking up without having recharged.

You may have enough energy to get dressed but not enough for the shower as well. You may be able to walk to the shop but struggle to think clearly afterwards. A conversation can feel surprisingly demanding. Something you managed yesterday may seem impossible today.

And perhaps most confusingly, the amount of effort does not always seem to match the consequences.

That is one reason Long COVID fatigue can be so difficult to explain to other people. From the outside, the activity may look small. Inside the body, researchers are finding that the response to exertion can be very different.

This does not mean every episode of fatigue is caused by dysfunctional mitochondria. But altered energy metabolism may be one reason researchers are looking beyond explanations such as ordinary tiredness or simply being out of shape.

Why Can You Feel Worse After the Activity?

One of the strangest features of Long COVID is that you can sometimes do something and think you have got away with it.

Then the worsening arrives later.

You may feel heavier, weaker or flu-like. Brain fog may increase. Pain, dizziness, sleep problems or other symptoms can flare. For people who experience post-exertional malaise (PEM), this delayed worsening can last for days or sometimes longer.

This is important when thinking about mitochondria because the question is not simply:

“Can the body produce enough energy?”

Researchers are also asking:

“What happens to the body when that energy is demanded?”

The muscle findings after exercise are particularly interesting for this reason. They suggest that, at least in some people with Long COVID, exertion may trigger biological changes that are not what we would expect from ordinary exercise fatigue.

That does not yet tell us exactly why PEM happens. But it helps explain why advice to simply “push through” can be so inappropriate for someone whose symptoms worsen after exertion.

So Should You Try to “Boost” Your Mitochondria?

This is where things become much less certain.

If mitochondrial dysfunction may be involved, it is tempting to think that the solution must be to increase mitochondrial function. Online, that can quickly lead to supplements, special diets, fasting, exercise programmes and products promising to “restore cellular energy”.

The biology is not that simple.

At present, there is no established treatment that has been shown to correct mitochondrial dysfunction and resolve Long COVID.

That does not mean nutrition or other aspects of health are irrelevant. It means we should distinguish between supporting general health and claiming that something treats the underlying mitochondrial changes being investigated in Long COVID.

A balanced diet that provides adequate energy, protein and micronutrients is sensible. But there is currently no specific “mitochondrial diet” proven to treat Long COVID.

The same caution applies to supplements. Compounds such as CoQ10 and others involved in cellular energy metabolism have attracted research interest, but evidence for treating Long COVID remains limited. Supplements can also interact with medications or be unsuitable for some people.

“Supports mitochondrial health” is not the same as “has been shown to treat Long COVID.”

That distinction matters.

What About Exercise?

For someone with Long COVID, this question needs particular care.

In many conditions, gradually increasing exercise is helpful. But if you experience PEM, repeatedly exceeding your energy limits can make symptoms worse.

So the goal should not automatically be to train your mitochondria harder.

For some people, gentle movement within their current capacity may be manageable. For others, even a short walk or standing activity may already exceed what their body can tolerate.

The useful question is not:

“How much exercise should I be doing?”

It is:

“What level of activity can my body currently tolerate without causing a significant worsening afterwards?”

That limit can include cognitive and social activity as well as physical movement. Reading, concentrating, working at a computer or having a long conversation can all require energy.

If activity consistently causes delayed worsening, recognising that pattern and learning to pace within your current limits can be more useful than repeatedly trying to push through it.

And needing to do that is not a failure of motivation.

It is responding to the body you have today while researchers work to understand why its response to exertion has changed.

→ Read more: Post-Exertional Malaise: Why Symptoms Worsen After Activity