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The victim was found with stab wounds in Friars Wharf last night and later died from his injuries.
He is believed to be a 16-year-old boy from Birmingham.
Cops have now arrested a 25-year-old man and a 33-year-old man, both from Oxford, on suspicion of murder.
One eyewitness said he saw the victim lying under a bridge in “a pool of blood”.
He told the Oxford Mail: “There were three or four runners trying to revive him, he had stab wounds in his chest and I think he was dead.
“There were no police there and an ambulance was on its way.
“I jumped off my bike to try and help and the runners were trying to revive him. They did not know what had happened.”
Officers have cordoned off the scene as the investigation gets under way.
Detective Chief Inspector Andy Howard, of the Thames Valley Police Major Crime Unit, said: “We are in the early stages of this investigation but we have already made two arrests.
“I understand that this incident will cause concern in the community, but I would like to reassure people that we are carrying out a full and thorough investigation.
“Members of the public can expect to see an increased police presence in the area in the coming days while our officers make enquiries.”
Anyone with information should call Thames Valley Police on 101.
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