The Highlanders struggled to overcome the late withdrawal of Waisake Naholo, as they slumped to a 38-29 loss to the Lions in Johannesburg on Sunday (NZ time).
The All Blacks winger was withdrawn by the coaching staff who decided he needed another week to recover from his knee injury.
The Highlanders and Lions managed to score five tries each, though Aaron Mauger's side were hammered 12-3 in the penalty count by South African referee Rasta Rasivhenge.
The Highlanders trailed 14-12 at halftime and the Lions extended their lead when flanker Kwagga Smith burrowed over for this second try after 52 minutes.
Jordan Hyland scored his first Highlanders try four minute later, before Aaron Smith helped the visitors regain the lead with a break to set up Matt Faddes.
Eltjon Jantjes slotted a penalty soon afterwards before replacement Shaun Reynolds scored a try.
Josh Ioane scored at the base of the post with five minutes to go but a crucial knock-on by Sio Tomkinson allowed the Lions to use their scrum dominance to put Courtnall Skosan over for the game's final try.
That score robbed the Highlanders of a bonus point and capped off a disappointing afternoon that had started brightly.
The Highlanders next meet the Stormers in Cape Town. They return to a bye after the Stormers trip, before finishing the regular season at home against the Bulls and Waratahs.