The 1991 eruption of Mount Pinatubo had dramatic effects on the regional climate in the Middle East. Though acknowledged, these effects have not been thoroughly studied. To fill this gap and to advance understanding of the mechanisms that control variability in the Middle East's regional climate, we simulated the impact of the 1991 Pinatubo eruption using a regional coupled ocean-atmosphere modeling system set for the Middle East and North Africa (MENA) domain. We used the Coupled Ocean-Atmosphere-Wave-Sediment Transport (COAWST) framework, which couples the Weather Research and Forecasting Model (WRF) model with the Regional Oceanic Modeling System (ROMS). We modified the WRF model to account for the radiative effect of volcanic aerosols. Our coupled ocean-atmosphere simulations verified by available observations revealed strong perturbations in the energy balance of the Red Sea, which drove thermal and circulation responses. Our modeling approach allowed us to separate changes in the atmospheric circulation caused by the impact of the volcano from direct regional radiative cooling from volcanic aerosols. The atmospheric circulation effect was significantly stronger than the direct volcanic aerosols effect. We found that the Red Sea response to the Pinatubo eruption was stronger and qualitatively different from that of the global ocean system. Our results suggest that major volcanic eruptions significantly affect the climate in the Middle East and the Red Sea and should be carefully taken into account in assessments of long-term climate variability and warming trends in MENA and the Red Sea.