The 20-year-old wore the captain's armband as the Blues faced Erik ten Hag's side at Old Trafford, starting at left-back once again, but it proved to be a frustrating night for the defender and his team-mates.
Although Robert Sanchez kept out Bruno Fernandes' early penalty, United eventually made their dominance count as Scott McTominay scored either side of a Cole Palmer equaliser to leave Chelsea tenth in the Premier League table and already 11 points off the top four.
Mauricio Pochettino admitted that the 2-1 defeat was a "fair" result, with his side comfortably second best, and he suggested Chelsea went into the match tired after playing against Brighton with ten men for 45 minutes last weekend.
Colwill cut a more frustrated figure though, believing McTominay's second goal, a header that proved to be the winner, should have been ruled out. McTominay shrugged off Colwill at the back post to get on the end of Alejandro Garnacho's cross, and VAR checked to see whether the Scottish midfielder had committed a foul.
The goal stood as it was deemed that there was not enough contact on Colwill, who felt a penalty would have been given had the roles been reversed.
"VAR has something against me right now, I don't know what I've done to them," Colwill said.
"Against Brighton they tried to give a pen, and then when I got pulled [by McTominay] they didn't give anything. If I had pulled him like that they would have given a penalty. It is what it is.
"It was a frustrating night. We had chances that if we'd taken would have made the game quite different, but it's part of the game and we'll move on from it come the weekend against Everton."