Where does fatique come from?

I personally feel the worst fatigue comes from a bad mid range followed by a harsh high end. Again I think speakers are the first consideration when trying to battle fatigue. Followed by the source then pre-amp/amp - receiver - int amp. It's actually a combination of all things from your room to power cables and interconnects. So again I think the best place to start battling fatigue is in the speakers. As far as how much - that's what ever you can afford to relieve the fatigue. An example my second set of speakers were the BIC formula 4's {$229 retail)(about 30 years ago). They were extremely bad in the mid's but had what I thought was great bass. Then I got the mission/cyrus 782's ($800 full retail 21 years ago). No they didnt have the bass of the formula 4's but the fatigue was gone. The mids and highs were a world better. Now I have the Dynaudio C1's {$7450 retail}(and demoing the C2's ($13,000 retail) as I type). The Mission/Cyrus never fatigued me so to speak but the Dyn's sound so much better to ME. Some people do not care for the Dyn's. Another example is my son has Klipsch kfl-30's. They have decent bass (although slightly muddy to me) but an IN YOUR FACE mid range which I can't take for much more than an hour. He loves them and I don't. So yes it an individual thing along with the equiptment and what you can afford. In home demo is my highest recommendation for any componets you may be thinking about.

An untreated room (no acoustical panels) can sound fatiguing, especially if your speakers are bright.

My recently treated listening room sounds great now, but before I could only listen at low volume for short periods of time.

Panels (ATS Acoustics, GIK etc) are inexpensive and make a huge difference.

Distortion is very fatiguing.

I believe it varies with the person involved.

Think about other situations that are fatiguing, such as driving at night in the rain. You have to concentrate at a very high level to correctly interpret what you see. The paint lines between lanes are hard to see, there is a lot of glare from oncoming headlights and visibility is just downright poor. Your brain can expend a lot of processing power to "correct" the information it is receiving. Most people feel absolutely drained after a long drive in those conditions.

Same thing with concentrating on a difficult test where a minor misreading of a test question could lead to a wrong answer.

Our brain has an amazing ability to sort through the information it receives (think of concentrating on one conversation in a noisy room), but that effort comes with a price tag attached. The harder it has to work the faster we feel worn down by the task at hand.

It is no different with listening to music. However, different people listen for different things. A particular overemphasis or deficiency may bother one person (and thus require more mental correction) more than it bothers another.

As an example, one listener may value midrange tonal accuracy more than good bass. Good bass with a inaccurate midrange will annoy that listener while another listener may be blase about a slightly off midrange yet strain mightily to supply the missing info to a bass line that is important to him. There are obviously a wide variety of parameters for each listener to prioritize in a fashion that is important to them.

That said, some errors are more likely to bug a high percentage of listeners. Edgy distortions probably top the list of near universal annoyances, but even then we all know people who are perfectly happy with their table radio with the blown speaker.