The Queensland Reds backrow powerhouse was named on the bench for the Test match at Loftus Versfeld.
But he injured his back when Nathan Sharpe fell on him in a training session and the Wallabies are now sweating on his fitness.
The Wallabies, who sit second in the table, are willing to wait until the last minute before making a decision but it has been reported that Higginbotham is unlikely to recover.
If he is not passed fir to play the Wallabies will switch to a 4-3 split between forwards and backs on their bench with fly-half-cum-centre Mike Harris slotting in.
It is just the latest injury blow to hit the 19-cap flanker in Pretoria. Two years ago he pulled out of his Test debut due to back spasms.
But he has become a major feature in the Wallabies set-up and is likely to face the Lions during next year's tour.