The Portuguese midfielder missed Saturday's 2-1 win over Exeter with a pelvic injury and is still struggling.
Semedo's absence meant Parkinson had to make a change to his line-up for the first time this season, having named the same starting XI for eight consecutive league matches.
Matt Spring came into the midfield and is likely to keep his place if Semedo misses out again.
Parkinson, who managed Colchester to promotion to the Championship in 2006, could have a dilemma in attack after former U's loanee Izale McLeod climbed off the bench to score the winner on Saturday.
Midfielder Dean Sinclair is still missing with a knee injury.