I think I had a similar problem about a month ago. In one workout, I did a typical workout with back squats (probably 4x5 or near that). I have a major muscle imbalance in my right leg stemming from an ankle injury, surgery, etc. Anyway, after the squats, I did 3 extra sets of right leg squats. They felt fine, pretty loose but about an hour afterwards I was in some serious pain (just soreness really). So, I pretty much figured I just overtrained and took an extra day off.
Three days later I went to do some front squats and could barely get one rep out of my warmup set. Actually both my hamstrings felt pretty tight so I skipped my legs that day and a few days later I was back at it.
I think this all really stems from the imbalance. When I watch myself squat in a mirror, I can see my left leg doing most of the work on the last rep. So I pretty much forced my right leg to failure, then used my left leg for one more rep which took it to failure also. So 4-5 sets of that sounds like serious overtraining.
I would recommend that you examine your calfs, quads, hammies very closely for an imbalance. Also, get right up close to a mirror and do a set of squats and see if you are favoring one side or the other. Something else may very well be going on, but maybe your problem is similar to mine.
Best of luck.