The veteran defender, out of contract at the end of the campaign, is expected to be out for up to three months after he was hurt in the closing stages of Saturday's match at Loftus Road.
Dunne was forced off with seven minutes, with a defensive reshuffle preceding Sadio Mane snatching an injury-time winner for Southampton in QPR's first game since the resignation of manager of Harry Redknapp.
A QPR statement on Sunday read: "Defender Richard Dunne is set for a prolonged spell on the sidelines owing to a knee injury.
"The Irishman sustained a medial cruciate ligament injury to his right knee in the R's 1-0 defeat to Southampton on Saturday and is expected to be out for up to three months."
Fellow centre-half Nedum Onuoha, the player Mane held off to score Southampton's winner, will also be unavailable for QPR in the near future.
Onuoha injured a hamstring against Southampton and is likely to be sidelined for three to four weeks.
However, there was one piece of positive news for QPR on Sunday, when it emerged that Charlie Austin's foot injury is not as serious as first feared.
