The Irish star lasted less than 90 seconds of the opening Test in Christchurch, which ended in a 21-3 defeat for Sir Clive Woodward's side.
O'Driscoll was stretchered off after a challenge by All Blacks hooker Keven Mealamu and captain Tana Umaga which Woodward labelled a 'double spear-tackle'.
Both players were cleared of any wrongdoing by match commissioner Willem Venter but the repercussions for O'Driscoll look like being longer-lasting.
An update from the Lions camp revealed: "A scan earlier this morning (Sunday) in Christchurch on Brian's right shoulder showed significant soft tissue damage around the joint.
"It is likely, though not certain, that he may require surgery. The inflammation around the joint needs to settle prior to determining appropriate surgical management.'
After O'Driscoll's early exit, flanker Richard Hill twisted his knee to join Tom Shanklin, who suffered a knee injury in training, on the sidelines.
On Hill, Woodward added: "Richard Hill has suffered a very serious injury. He had a scan and he's ruptured his ACL (anterior cruciate ligament) which is a recurring injury for him. It is is potentially career-threatening in terms of rupturing an ACL.'