According to Suffolk County police, the accident took place at 6:18 a.m. in the eastbound land of the LIE, between exits 63 and 64 in Medford.
Suffolk County Police Sixth Squad detectives are investigating the accident.
Police said a Riverhead woman, 32, was driving a 2007 Kia eastbound when her vehicle struck a 2002 Ford van, which was stopped and pulled off to the shoulder.
The driver of the Kia was transported to Brookhaven Memorial Hospital Medical Center in East Patchogue for non-life-threatening injuries. Her passenger, a 33-year-old Riverhead man, was also transported to Brookhaven Memorial Hospital Medical Center for serious injuries, police said.
The driver of the van, a 49-year-old Nesconset man, was not injured, police said.
Both vehicles were impounded for safety checks and the investigation is continuing.
The identities of those involved in the accident have not yet been released by police.
Police are asking that anyone who may have witnessed the crash to contact the Sixth Squad at 631-854-8652 or call anonymously to Crime Stoppers at 1-800-220-TIPS. All calls will remain confidential.