State department spokesperson Jen Psaki said on Wednesday that the US has no independent confirmation of reports of a second American killed while fighting with the militant group. "We're looking into it", she said.
NBC cited an anonymous member of the opposition Free Syrian Army as saying two Americans have been killed in a battle last week with Islamic State fighters.
The US confirmed the death of one American, Douglas McAuthur McCain, who grew up outside Minneapolis in the town of New Hope and most recently lived in San Diego.
A relative, Kenneth McCain, said that the state department called to tell his family that Douglas McCain had been killed in Syria. "We do not know if he was fighting anyone", he said.
Investigators were aware that McCain was in Syria to fight with the militant group, said a US official who was not authorised to discuss by name an ongoing investigation and spoke only on condition of anonymity.
Surveillance flights have begun over Syria on the orders of President Barack Obama, a move that could pave the way for airstrikes against the Islamic State group.