The luckless Slade, who has won 10 New Zealand caps as understudy to Dan Carter, had an operation on his injured left leg in Canberra on Sunday and will play no further part in the season.
Slade missed much of the last Super Rugby season when he broke his jaw twice and when Carter was ruled out of the World Cup last October, a groin strain of his own prevented the 24-year-old from making the most of his opportunity.
With his back-up Liam Sopoaga also ruled out for a lengthy period with a shoulder problem, Highlanders coach Jamie Joseph faces a desperate scramble to find another flyhalf before their match against the Melbourne Rebels on Friday.
Adding to his problems, flanker John Hardie was also condemned to a long period on the sidelines after breaking his toe and missing the 33-26 defeat to the Brumbies, which brought an end to their impressive run of four wins to start the season.
"It's pretty horrific, really," Joseph told the Otago Daily on Monday.
"We don't do things by halves in the Highlanders. The one thing I know about this group of guys is they are pretty tough. They'll bounce back.
"It's a long season. We've had a great start but now we've got to deal with some tough issues.
"I'm pretty proud of our guys. I think they've created something quite special down here."
The Highlanders also started last season well but faded to finish eighth and miss out on the playoffs.