Listening fatigue

My first instinct is to agree with Elizabeth's guess that the sub is the first culprit.

Is there a low pass filter on the sub? Where is it set? Is it self powered? What volume are you playing it at? Setting a self powered sub's low pass filter too high and especially too loud will definitely cause fatigue with any component set-up. You'll probably cure the problem by setting the system up "flat".

Remove the sub for a few days,and see if that works,sometimes subs cause more problems than they are worth.

Funny, I experienced fatigue just a couple of nights ago for the first time in ages. I was listening to vinyl at a very reasonable volume.

"as always, YMMV"

I played in bands off and on for years and I would never (now, at least) want to recreate those levels of sound pressure in my private listening. Those guys at the soundboard have made themselves deaf and are gradually doing the same to you.

Another thing that is well-known for causing listener fatigue is odd-ordered harmonics in trace amounts, something that is common to most transistor gear.

This will get more pronounced as volume is increased.

The reason is that the ear uses odd ordered harmonics to figure out how loud a sound is! If the equipment makes odd ordered harmonics it will come off as louder and brighter than the measurements would suggest.

Our ears are more sensitive to these harmonics than they are to human vocal frequencies- by quite a wide margin!

To get rid of the odd ordered harmonics, you might try introducing some tube electronics into the signal chain. Tubes are more linear, and make less odd ordered harmonics as a result. This is why they sound smoother in most cases.