The double tragedy on the outskirts of the city came hours after an 18-year-old female student was killed in another crash in Co Cork.
Gardaí, meanwhile, have appealed for witnesses to the accident at 12.05am yesterday which claimed two lives, a 25-year-old mother-of-one from Cork and a 17-year-old male driver from Wexford.
It is believed a number of witnesses have already come forward.
The collision occurred on a national primary route, the N25 between Midleton and Cork.
Preliminary reports suggest one of the cars was driving in the wrong direction at the time of the crash.
Both drivers reportedly died instantly. The dead were named locally as Aoife Callanan and John Joe Galvin.
The accident occurred just 800m on the Midleton side of the Little Island junction.
A 23-year-old man, who was a passenger in the 17-year-old’s Volkswagen Golf, remains in Cork University Hospital where he was said to be in a serious condition.
Ms Callanan, the mother of a four-year-old girl Sadhbh, was originally from Ballincollig. It is understood she had recently relocated to the East Cork village of Dungourney. She worked in the accounts department at Amazon.com in the Cork Airport Business Park.
Mr Galvin lived at Ballymitty, Co Wexford. He and a friend were on their way to attend a car rally taking place this weekend in West Cork.
All the Wexford competitors and volunteers from that county assisting at the Clonakilty-based event yesterday withdrew as a mark of respect.
The city-bound section of the dual carriageway was closed off for several hours as garda crash scene investigators examined the scene.
Supt Pat Lehane, who is leading the garda investigation, offered his sympathy to the families of the deceased.
“We are still awaiting the full results of our technical examination to determine how the accident happened,” he said.
He said some motorists who were travelling along the road when the accident happened had already contacted gardaí.
“We know there were more motorists there who have yet to come forward and we’re appealing for them do so. We would like to speak to anybody who was in the general vicinity between 11.45pm and 12.05am and who may have seen any of the two cars,” he said.
Anybody with information is asked to contact Cobh Garda Station at 021-4908537.