Smith has been ruled out for six to eight weeks with a high hamstring injury.
Smith (32) picked up the injury in the last 10 minutes of the side's draw with the Chiefs on Saturday night.
Highlanders assistant coach Glenn Delaney confirmed Smith was out for this period and said it was a blow to Smith and the Highlanders team. The side would look to play Matt Faddes or Josh McKay at fullback.
The team has five games left in the regular season and with the final game of the season before the playoffs set for June 14, it may be touch and go whether Smith gets back for the Highlanders. The team is seventh in the Super Rugby standings and is in with a chance of making the playoffs.
He was forced off the field after the injury on Saturday night and there were initial fears it was a serious knee injury but it turned out to be his hamstring.
Smith, who has played more than 150 games for the Highlanders, is playing his final season with the Highlanders before heading to France after the World Cup to play for Pau.