Orpik, who returned to the Penguins' lineup Wednesday night after missing five games with an undisclosed injury, did not play after the first period of action.
He was caught on the ice for a lengthy shift of 1:36 with the Rangers enjoying some extended time in the offensive zone and did not look well after the sequence. He played only two more shifts for a combined 42 seconds after that and never returned to the Penguins bench after the first intermission.
The Penguins won the game, 4-2, to take a 3-1 lead in the series.
Should Orpik miss Game 5 in Pittsburgh on Friday night, rugged blue-liner Robert Bortuzzo likely will draw into the lineup.