1. Death of Stonewall Jackson a few days after the battle.
2. Dissension about whether to invade Pennsylvania in search of food and war supplies, or send troops West to stop Grant liberating the Mississippi.
(3rd, not realised at the time)
It was now that Lee's health started to fail, possibly from the shock of losing Stonewall, and he was unwell during the fateful Battle of Gettysburg.