Police initially said one person had been seriously injured and a helicopter was responding to the scene. A second person suffered moderate injuries.
As of 6.30pm a person remained in a serious condition in Waikato Hospital's high dependency unit, a DHB spokeswoman said.
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The crash is in almost exactly the same spot where a person was killed in a crash on December 30.
The crash came just 40 minutes after a car and a motorbike collided at the intersection of SH3 and Kuratahi St in Piopio.
One person was reported to have moderate injuries and another minor injuries.
SH3 is closed and diversions are in place at Ruru St, Piopio to the south, and Tikitiki Rd to the north.
Police asked motorists to be patient and to take care.
Late on Sunday afternoon a further crash in Tapapa, South Waikato left three people hurt, one seriously.
A police spokeswoman said it appeared a car had gone off Somerville Rd and into a fence just before 4.25pm. There were reports of one person trapped, with fire and ambulance attending the incident.
DEADLY WEEKEND
A total of eight lives have been lost on North Island roads this weekend.
As well as this afternoon's crash in Piopio, at 2.15am three people were killed and a child was critically hurt after their car smashed into a tree near Whananaki in Northland.
On Saturday three crashes in Waikato had already left four people dead.
Two people lost their lives in a crash on Cambridge Rd, in Leamington, south of Cambridge, about 6pm last night. However a witness told Stuff a baby had survived the crash, which involved a small logging truck and another vehicle.
Earlier, a person died in a two-vehicle crash in Tahuna, 18km north of Morrinsville at 10.30am.
And on Saturday night a fourth person died when their vehicle crashed into a power pole on State Highway 25 near Pipiroa, 15km south-west of Thames.