The crash happened early Monday around 12:30 a.m. on the southbound lanes of SH 288 in Rosharon.
Sgt. Woodward with Texas DPS says a total of four vehicles were involved in the crash that appeared to be caused by a wrong way driver.
The two people were confirmed deceased at the scene, according to DPS.
Officials have not determined which vehicles the deceased occupied and did not say if anyone else was injured.
DPS was able to clear the crash and reopen the highway around 7:30 a.m.
Check out our interactive traffic map to see other trouble spots across the Houston area:
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