Helicopters Otago managing director Graeme Gale said for rescue helicopter staff the South was "not the happiest place to be".
Emergency services were called to the two-vehicle crash on State Highway 8 near Omarama at 10.19am, police said.
One person died and two were transported by helicopter to Dunedin Hospital - one was in a critical condition and one was in a moderate condition.
The road was closed while the Serious Crash Unit completed a scene examination, police said.
Fire and Emergency New Zealand shift manager Bailey Wells said several crews from Twizel, Omarama and Otematata responded to the collision.
Three helicopters, a first response unit, a prime doctor and two ambulances attended the scene.
About 11.40am emergency services were alerted that a 10-year-old Australian girl on holiday with her family fell into the fast-flowing Marian Creek, which joins the Hollyford River in Fiordland National Park.
Police said the girl was found and removed from the water a short time later.
CPR was performed and a doctor was flown to the scene.
"Sadly, however, she was unable to be revived," Southland area commander Inspector Mike Bowman said.
He thanked everyone involved in the "traumatic event", in particular members of the public who helped find and provide assistance to the girl.
Helicopters Otago attended both incidents.
"Like any accident we go to, it doesn’t matter whether it was yesterday, last week or the day before, our staff are human and they take it seriously and it does affect people," Mr Gale said.
"We’re there to preserve life and provide the best possible chance of life.
"When you are fighting to keep someone alive, it is tough because everyone has family or friends, brother and sisters, or mum and dad, [and] we often relate to our own circumstances."
His staff had some "serious upskilling", were very professional and at the top of their game in the medical field.
"Over Omarama way we had three crews and three different machines. It’s just not the happiest place to be.
"We go and try to reverse what was a serious outcome, and ... unfortunately sometimes we just can’t do that."
