Two men, one from Islamorada and one from Hialeah, died at Mariners Hospital after their vehicles collided head-on at mile marker 78 on U.S. 1.
The Florida Highway Patrol identified the dead as John S. Esslinger, 64, of Islamorada, and Manuel Navarrete, 44, from Hialeah.
According to an FHP report, Navarrete's 2015 Lexus IS 250, which was traveling south around 10 Friday night., drifted into the northbound lane of U.S. 1, striking the left front side of Esslinger's 2014 GMC Yukon.
A 2007 Cadillac Escalade driven by Antonio Luis Llambes, 57, of Miami, was traveling directly behind Navarrete's vehicle and struck it as he tried avoiding the crash. Neither Llambes or his passenger, Maria Llambes, 60, were seriously injured.
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Esslinger's passenger, Patricia Lynn Stanley, 60, was injured and taken to Kendall Regional Hospital. She is expected to recover, said FHP Sgt. Pedro Reinoso.
First responders took Esslinger and Navarrete to Mariners Hospital in Tavernier, where they were both pronounced dead.
U.S. 1 was blocked off as FHP troopers investigated the crash and reopened to traffic at 1:50 a.m. Saturday.
Charges are pending, according to the FHP.