Barrett fouled off a 1-1 pitch from Colorado starting pitcher Ubaldo Jimenez and quickly fell to the ground.
Barrett was attended to by the Padres' training staff and walked off on his own, though he had blood on his face after the foul ball appeared to hit under his helmet before hitting his nose.
Barrett was replaced in the game by Luke Carlin. The Padres don't have a third catcher on their roster, though second baseman Edgar Gonzalez worked out at catcher in Spring Training.
Barrett was taken to a nearby hospital for further evaluations. The preliminary diagnosis was a fractured nose.
Barrett, who missed a month of action early this season with a strained right elbow, entered Wednesday's game against the Rockies hitting .202 with two home runs and nine RBIs.
San Diego manager Bud Black said that Barrett will remain behind in Denver on Wednesday while the team flies to Phoenix to start a three-game series with the Diamondbacks on Friday. Black also said that Barrett was to have a CT scan at some point Wednesday.
Black said a disabled-list stint for Barrett might be in order and that Nick Hundley will likely be recalled from Triple-A Portland to take Barrett's spot on the 25-man roster.
Corey Brock is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.