Landscape-scale Barred Owl (Strix varia) management to support Northern Spotted Owl (NSO) (S. occidentalis caurina) recovery has provided a unique opportunity to investigate a wide array of disease and toxicological threats to barred owls, but more importantly, to their close, but threatened relatives, NSO, and other native wildlife. In this study, we tested livers from 765 Barred Owls collected in northwestern California for 14 compounds, including 12 anticoagulant rodenticides (AR)—seven first-generation (FGAR) and five second-generation (SGAR)—as well as two non-anticoagulant rodenticides, bromethalin and cholecalciferol. Using replicate-averaged concentrations with adjustments for detection limits, 46% of owls showed exposure to at least one rodenticide, with 36% exposed to AR. SGAR dominated detections (36%), particularly brodifacoum (31%) and bromadiolone (15%), while FGAR exposure remained low (0.9%). Mean concentrations among exposed owls were 17.3 ppb (range 1.0–446 ppb). Statistical analyses revealed significantly lower exposure probability, compound count, and concentration in males relative to females and declining exposure with younger age classes. Spatial effects by latitude were weak overall but significant for cholecalciferol concentrations. These findings indicate persistent, widespread SGAR contamination in regional owl populations despite regulatory restrictions, with demographic disparities suggesting behavioral or trophic exposure differences.