Orient goalkeeper Jamie Jones went down in a first-minute melee in which the ball was scrambled off his line, and was stretchered off after receiving lengthy treatment.
The O's survived intense pressure during the opening 20 minutes. Striker Kayode Odejayi saw a header drift wide, while the visitors survived a goalmouth scramble in which goalkeeper Ben Williams plunged at the feet of striker James Scowcroft.
Orient's replacement keeper Glenn Morris made a superb save to deny midfielder John-Joe O'Toole as the second-half started brightly.
Colchester broke the deadlock through Odejayi's header on 54 minutes after a flick-on from Anthony Wordsworth's corner.
The U's survived a free-kick in their own penalty area and Williams had to tip over a fierce drive from midfielder Andros Townsend for what was only Orient's second corner six minutes from the end.