This study tested whether amphipods (Crangonyx spp.), traditionally thought to be detritivores, prey on Northern Red-legged Frog (Rana aurora) embryos at the Humboldt Bay National Wildlife Refuge in California (HBNWR). Following observations that amphipods were associated with the disappearance of frog embryos, we performed experiments in which embryos were placed in 1 of 4 treatments: chambers open to all predators; screened chambers allowing access by small predators <1.5 mm in diameter (including amphipods); enclosed chambers with all visible predators excluded; and enclosed chambers with amphipods added and all other visible predators excluded. Trials with the first 2 treatments were repeated at a nearby site with no amphipods (BL). We found that average predation rates on viable embryos were similar among open/screened chambers at HBNWR and open chambers at BL (21–32%), whereas the average predation rate in amphipod-addition chambers was 15%. Egg-loss rates were ≤1% for amphipod-exclusion chambers at HBNWR and screened chambers at BL. We conclude that embryo predation by amphipods does occur and has the potential to be as important a mortality factor as predation by other larger predators. However, the significance of this interaction is likely to be highly context-dependent and affected by factors such as amphipod density and food availability, and the size and cohesiveness of egg masses.