Increased frequencies of physiological episodes have been a significant concern for Naval Aviation for the last several years. These include several aircraft platforms, but no previously documented E-2D Hawkeye events. This report documents an episode in an E-2D, with multiple aircrew affected at the same time. While deployed aboard a U.S. aircraft carrier, five E-2D Hawkeyes aircrew were simultaneously exposed to the same over-pressurization during a routine sortie. Out of the five aircrew, four immediately reported hypoxic-like neurocognitive symptoms of mental slowing, difficulty concentrating, and headache. They were evaluated and treated using standard protocol according to the Physiologic Event Clinical Practice Guidelines set by the Naval Safety Center. All aircrew were treated with 100% ground level oxygen with resolution of symptoms. Although rare, physiological events may occur in multipassenger platforms such as the E-2D Hawkeye. Utilizing and strictly adhering to standard clinical practice guidelines provided an efficient process of evaluation by different flight surgeons concurrently that avoided a possible delay in treatment. After, eliminating other potential etiology for the crews symptoms, a pressure-related mechanism of injury appears to be the most probable cause.