It happened just before 6 Sunday morning on Santa Fe Drive, west of Franklin Road.
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The California Highway Patrol says a 34-year-old man from Merced was driving a Jeep westbound and for an unknown reason, went into the eastbound lanes.
It hit a Nissan driven by a 38-year-old woman from Turlock.
The crash killed the two, plus a 34-year-old woman in the Jeep.
Officers say she was in the backseat and wasn't wearing a seatbelt.
They say the roadway doesn't stand out for being unsafe, but it is heavily traveled.
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"A lot of people use it to commute to avoid Highway 99 right now because of construction, but we get a fair number of crashes there," says CHP Officer Eric Zuniga. "It's a pretty busy roadway."
Officers have not publicly identified the victims and they're still investigating what led up to the collision.
They say they're looking into whether drugs or alcohol played a role.