To predict how future climate scenarios may impact sub-tropical nearshore fishes we examined blood-based physiological responses of three fish species to a suite of seawater conditions associated with future climate change. We chose Bonefish Albula vulpes, Yellowfin mojarra Gerres cinereus, and Checkered puffer Sphoeroides testudineus because they are common in sub-tropical and tropical mangrove ecosystems throughout the Western Atlantic and important to the local fisheries. Fish were exposed to an acute (30 minute) increase in salinity (50 ppt), acidity (decrease in pH by 0.5 units), or temperature (7-10°C), or temperature and acidity combined, and held in these conditions for 6 hours. Their physiological responses were compared across seasons. Bonefish exposed to challenges in the summer experienced greater blood-based osmotic and ionic disturbances compared to fish held in ambient conditions, with thermal challenges (particularly in the summer) being the most challenging. No significant treatment effects were observed for Yellowfin mojarra or Checkered puffer in either season. Together, results from this study demonstrate that acute climate-induced changes to thermal habitat will be the most challenging for sub-tropical fishes (particularly in the summer) relative to salinity and pH stressors, but significant variation across species exists.