Another 27 people were injured, six seriously, when a truck's container crashed into a bridge and then spun down onto the tourist bus, the report said.
The tourists were on their way to the central city of Trinidad at the time.
The dead in the crash late Saturday in Sancti Spiritus province were Cuban driver Alkier Barrera, 37 and a 64-year-old German tourist whose identity was not immediately given.
Trinidad, which has much of its Spanish-colonial era architecture intact, is among the most popular tourist attractions in central Cuba.