An expanding body of research indicates that exposure to contaminants may impact marine mammal health, thus possibly contributing to population declines. The harbor seal population of the San Francisco Bay (SFB), California, has suffered habitat loss and degradation, including decades of environmental contamination. To explore the possibility of contaminant-induced health alterations in this population, blood levels of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs) were quantified in free-ranging seals; relationships between contaminant exposure and several key hematological parameters were examined; and PCB levels in the present study were compared with levels determined in SFB seals a decade earlier. PCB residues in harbor seal blood decreased during the past decade, but remained at levels great enough that adverse reproductive and immunological effects might be expected. Main results included a positive association between leukocyte counts and PBDEs, PCBs, and DDE in seals, and an inverse relationship between red blood cell count and PBDEs. Although not necessarily pathologic, these responses may serve as sentinel indications of contaminant-induced alterations in harbor seals of SFB, which, in individuals with relatively high contaminant burdens, might include increased rates of infection and anemia.