Officers said the shooting happened at about 9:50 p.m. at Symphony Inn & Suites.
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Investigators believe the shooting happened inside of the motel room and continued outside on the second floor and ground level.
Several vehicles in the parking lot and walls of the motel room were seen with bullet holes, according to authorities.
Officials said a man and woman were shot during the incident. The woman was sent to the hospital in critical condition.
Police say they were many shots fired by the man who was shot and at least one suspect.
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The injured man fled the scene.
Investigators with the Houston Police Department said they are looking for him and the suspect(s). Detectives haven't said what motivated the shootout.