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The exchange of momentum, heat, moisture, and gas across the air-sea interface plays a crucial role in atmospheric and oceanic circulations on variety of spatial and temporal scales. That is why improved understanding and realistic simulations of air-sea flux are critical to advancing oceanic and atmospheric prediction capabilities. This study provides the first detailed analysis of oceanic and atmospheric responses to the current-stress, wave-stress, and wave-current-stress interaction at the Gulf Stream using a high-resolution three-way coupled regional modeling system. This modeling system allows for the exchange of data fields between the atmospheric model—Weather Research and Forecasting (WRF), the ocean model—Regional Ocean Modeling System (ROMS), and the wave model—Simulating Waves Nearshore (SWAN) through the Model Coupling Toolkit (MCT). We perform four one-month simulations for October 2012, a time period when the impact of wind and waves is relatively large. The four experiments differ in how wind shear and surface roughness length are calculated in the bulk flux parameterization: 1) The control experiment calculates the surface roughness length by using the surface wind only (no shear from currents). 2) The current experiment interactively takes into account surface currents in the wind shear. 3) The wave experiment explicitly includes the sea-state parameters in calculating the roughness length. 4) The current-wave experiment computes the surface roughness by taking into account the current-induced shear and sea state simultaneously. In general, our results highlight the substantial impact of coupling currents/waves with wind stress on the air-sea flux exchange and ocean upwelling over the Gulf Stream. Two-way coupling of waves and wind stress causes wind stress (30-day averaged) increase up to 12% in 95th percentile of the model domain, and increases greater than 5% are found in 50% of the model domain. For two-way coupling of surface currents and wind stress, both positive and negative changes in wind stress (greater than 5%) are found at the Gulf Stream, with only small changes elsewhere. The pattern of wind stress change in the wave-current-stress coupling experiment is similar to that in the current-stress coupling experiment, with over 15% increase of wind stress at the Gulf Stream. The current impact on wind stress cancels out the wave impact outside of the Gulf Stream in the wave-current-stress experiment. Coupling currents/waves with wind stress also change the wind stress curl, which impacts the response patterns of upwelling and downwelling in the upper ocean. Changes in wind stress and its curl due to coupling processes lead to changes in SST and ocean current in the Gulf Stream. Considerable SST change (in excess of 1 oC) and ocean current change (in excess of 0.2 m/s) are collocated near the SST front region in the shape of warm/cold core eddies in all coupling configurations. We perform a mixed layer heat budget analysis to investigate the physical processes happening in the ocean mixed layer and their contribution to the SST changes. Substantial latent heat flux changes exceeding 20 W/m2 and sensible heat flux changes exceeding 5 W/m2 are found over the Gulf Stream in all coupled configurations. Sensitivity test shows that SST-induced differences of air-sea temperature and humidity are major contributors to the LHF and SEN changes. The coupling processes also change the surface wind convergence, which further impacts precipitation.