All Black first five Colin Slade (leg) and in-form flanker John Hardie (toe) have both been scratched for the season, while tireless forward Nick Crosswell (knee) is out for six weeks.
Hardie's turf toe problem has been diagnosed as a break, and he will have an operation this week.
The luckless Slade had an operation in a Canberra hospital yesterday after suffering a badly broken leg in the Highlanders' 33-26 loss to the Brumbies on Saturday night.
It has been a wretched 18 months for Slade. He broke his jaw twice last year, was ruled out of the Rugby World Cup with a groin injury, and needed a hernia operation before this season started.
Slade's back-up, Lima Sopoaga, is also out for the season. His shoulder problem has been diagnosed as a fractured - in three places - scapula.
This puts immense pressure on Chris Noakes, the first-year player who has looked composed but is the only specialist No 10 left in the Highlanders.
Joseph was still digesting the Slade news yesterday and could not say where the Highlanders were going to find another pivot.
"I don't know, to be fair. In the next 48 hours we have to find another first five from somewhere.
"Anything's possible. We're going to have to scramble."
Phil Burleigh, an unexpected success at second five after being whisked into the squad six weeks ago, has some experience at No 10, as does fullback Ben Smith.
Wider squad first five Glenn Dickson has a wrist injury, while Hayden Parker (Otago) and Scott Eade (Southland) are in the franchise but are both very young.
The options around the country are limited, although Trent Renata, from Waikato, could be worth a look.
When the Highlanders suffered a similar playmaker crisis last year, they sent an SOS to Otago veteran Tony Brown. That would not be happening now, Joseph said, even if Brown had just returned to Dunedin to prepare to coach the Razorbacks.
"Tony is not an option this year. He hasn't been playing. Last year, he'd been playing in the top team in Japan and he was on the field."
Crosswell, who has been having a superb season, has a serious medial ligament tear.
Other long-term injuries include midfielders Kendrick Lynn (neck) and Siale Piutau (ankle).
"It's pretty horrific, really. We don't do things by halves in the Highlanders," Joseph said.
"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 have slipped to fifth in the Super 15 standings before their match against the Melbourne Rebels in Invercargill on Friday.
