The collision took place just after midday today on the A625 Hathersage Road towards Sheffield.
A cyclist riding a black Specialized bike appears to have lost control and come off the bike, colliding with a black Audi A4 travelling in the opposite direction.
The collision happened close to the junction with Sheephill Road.
A South Yorkshire Police spokesman said: "The cyclist, a 50-year-old man from Dronfield, suffered serious and potentially life-threatening injuries as a result of the collision. He currently remains in hospital.
"Anyone who saw what happened is asked to call 101 quoting incident 404 of August 18, 2018."