The evolution of intrinsic postzygotic isolation can be explained by the accumulation of Dobzhansky-Muller incompatibilities (DMI). Asymmetries in the levels of hybrid inviability and hybrid sterility are commonly observed between reciprocal crosses, a pattern that can result from the involvement of uniparentally inherited factors. The mitochondrial genome is one such factor that appears to participate in DMI in some crosses but the frequency of its involvement versus biparentally inherited factors is unclear. Here we assess the relative importance of incompatibilities between nuclear factors (nuclear-nuclear) versus those between mitochondrial and nuclear factors (mito-nuclear) in a species that lacks sex chromosomes. We used a Pool-seq approach to survey three crosses among genetically divergent populations of the copepod, Tigriopus californicus, for regions of the genome that are affected by hybrid inviability. Results from reciprocal crosses suggest that mito-nuclear incompatibilities are more common than nuclear-nuclear incompatibilities overall. These results suggest that in the presence of very high levels of nucleotide divergence between mtDNA haplotypes, mito-nuclear incompatibilities can be important for the evolution of intrinsic postzygotic isolation. This is particularly interesting considering this species lacks sex chromosomes, which have been shown to harbor a particularly high number of nuclear-nuclear DMI in several other species.