The collision, involving a car and a motorcycle, occurred on the N71 at Grillagh, north of Clonakilty.
The motorcyclist, a man in his 20s, was treated at the scene and taken by ambulance to Cork University Hospital.
The driver of the car, a man in his 70s, was also transported to hospital for assessment.
The road remains closed to traffic to allow for a technical examination by garda forensics, with local diversions currently in place.
Gardaí are appealing to anyone who may have witnessed the incident to come forward.
A spokespserson said: "Road users who were travelling on this stretch of the N71 around the time of the collision and who may have camera footage (including dash-cam) are asked to make it available to investigating Gardaí.
"Anyone with information is asked to contact Clonakilty Garda Station on 023 882 1570, the Garda Confidential Line on 1800 666 111, or any Garda station."
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