A large number of coastal ecosystems globally are subjected to concurrent hypoxic and acidified conditions that will likely intensify and expand with continued climate change. In temperate regions, the spawning of many important organisms including the Atlantic blue crab Callinectes sapidus occurs during the summer months when the severity of coastal hypoxia and acidification is the greatest. While the blue crab earliest larval stage can be exposed to co-occurring hypoxia and acidification observed in many coastal ecosystems, the effects of these concurrent stressors on larval blue crab survival is unknown. This study investigated the individual and combined consequences of low dissolved oxygen (DO) and low pH on blue crab larvae survival through a series of short-term experiments. During 14-day experiments with moderately hypoxic conditions (117–127 μM O2 or 3.74–4.06 mg L-1) and acidified conditions (pH on total scale of 7.16–7.33), low DO and low pH individually and significantly reduced larval survival by 60% and 49%, respectively, with the combination of stressors reducing survival by 87% compared to the control treatment (210–269 μM O2 or 6.72–8.61 mg L-1, 7.91–7.94 DO and pH, respectively). During 4-day experiments with lower DO levels (68–83 μM O2 or 2.18–2.62 mg L-1) and comparable pH levels of 7.29–7.39, low DO individually reduced survival by >90% compared to the control (261–267 μM O2 or 8.35–8.54 mg L-1, 7.92–7.97 DO and pH, respectively), whereas low pH had no effect and there was no interaction between stressors. Over a 4-day period, the DO threshold at which 50% of the larval blue crab population died (LC50) was 121 μM O2 (3.86 mgL-1). In 14-day experiments, the DO and pH effects were additive, yielding survival rates lower than the individual treatments, and significantly correlated with DO and pH concentrations. Collectively, these findings indicate that blue crab sensitivity to both low DO and low pH are acute within the larval stage, depend on the intensity and duration of exposure, and leads to mortality, thereby potentially contributing to the interannual variability and possible regional declines of this fishery.