For me, it's muscle weakness. Just sitting here at my computer I can raise my right leg about 3", the first time. Second time, a little less. After that, it's not coming off the floor. There, presto, I'm fatigued. Not all-over fatigued, but enough that if I get up and try to walk it will be noticeably more difficult than if I hadn't tried to lift my leg. That tiny action will show in everything I do until I rest for a few minutes.

Believe it or not, I can hike in the woods for over an hour. But my weakness would be way more advanced after that.