Hybridization produces a range of outcomes from advantageous to disadvantageous, and a goal of genetic research is to understand the gene interactions that generate these outcomes. Interactions between cytoplasmic elements, such as mitochondria, and the nucleus may be particularly vulnerable to accruing disadvantageous combinations as a result of their different rates of evolution. However, mitonuclear incompatibilities often do not have an observable effect until the F2 and later generations. We used Tigriopus californicus, a model system for mitonuclear incompatibilities that is also known for exhibiting heterosis in the F1 generation, to test whether hypoxia was more stressful for mitonuclear interactions than other environmental stressors. We generated 284 parental and 436 F1 hybrids from four population crosses (720 total) and compared parental and F1 populations for hypoxia tolerance. We observed that, on average, F1 hybrids were less likely to survive a hypoxia stress test than parental populations (Parental:F1 coefficients ranged from -0.04 to 0.14 with none significantly different from 0). This suggests that hypoxia may be a particularly intense stressor for mitonuclear coordination, and that hybridization outcomes vary by trait