Three people have now died following a crash on State Highway 8 near Pukaki today, police have confirmed.
Three others have serious injuries and a further two have moderate injuries, police said.
The crash involved two vehicles and a motorcycle and happened between Hayman Road and Tekapo Canal Road about 1.30pm.
A large number of emergency services staff, including three rescue helicopters responded.
"Despite the best efforts of those first at the scene, three people were unable to be saved," Inspector Craig McKay said.
"Several of the injured were trapped in the wreckage and needed to be cut out."
One of the deceased was riding a motorcycle while two others who died were travelling together in one of the cars, police said.
The fire chief who attended the crash scene said he is incredibly grateful for members of the public who were at the scene.
Twizel chief fire officer Simon Fox says an outstanding surgeon from Singapore and a Christchurch paramedic stepped in immediately.
"We came across a fairly chaotic scene today. Of course, there was heavy traffic which made it worse. It seemed all very closed in.
"We were fortunate enough that there were some very, very good bystanders before emergency services arrived there, tried to resuscitate people, and done some pretty good CPR work."
Fox said some nurses and volunteer firemen also happened to be travelling in the area at the time of the crashes.
"We are in the early stages of the investigation to determine what caused this tragic event," McKay said.
"The Serious Crash Unit is at the scene and their work will continue into the evening. A complex and lengthy investigation lies ahead of us."
"Crashes of this nature are incredibly confronting, and we are arranging support for those members of the public who were first at the scene and tried their best to save lives," McKay said.
"We can't thank them enough."
State Highway 8 will remain closed for some time and is not expected to reopen until late this evening.
Just 90 minutes after the fatal crash, there was a second three-vehicle crash a short distance away at the intersection of State Highway 8 and Tekapo-Twizel Road, police said.
One person received serious injuries and nine others suffered minor-to-moderate injuries.
Enquiries into the cause of the second crash are ongoing.
"We want to ask every motorist on the roads this weekend to take extra care," McKay said. "Please take your time, have plenty of breaks and drive to the conditions. Crashes like this show how easy it is for things to go horribly wrong."