The boys, aged six and eight, and a 44-year-old British man, were taken to hospital suffering “grievous injuries” said police in Malta.
Officers were called to the scene of the crash at around 4.15pm on Monday (April 9) in Valletta Road, Zurrieq.
A 37-year-old Spanish woman and a 62-year-old Belgian man were killed.
Three other people, a 31-year-old German woman, a 72-year-old Italian woman and a 35-year-old man whose nationality is yet to be established, were also hurt.
All six have been taken to Mater Dei Hospital for treatment.
Police said the double-decker bus struck a tree branch and that an investigation was under way.