We analyzed spatial and temporal variations in total mercury concentration (THg) in Mytilus californianus from the west coast of Baja California, México, and assessed the potential risk for human health. The sites from the northern zone showed the highest levels of THg over the entire three years of study, however, no significant differences among years were found. The highest level of THg (0.110 μg/g d.w.) was recorded in 2010 at Bajamar (SS2), and the lowest (0.011 μg/g d.w.) in 2007 and 2008 at Eréndira (SS4) and Los Ojitos (SS7), respectively. The estimated daily intake (EDI) values for adults through mussel consumption were lower than the oral reference dose (RfDo) and the acceptable daily intake (ADI) values established by the USEPA and the FAO/WHO, respectively. The target hazard quotient (THQ) values were <1.0, indicating that mercury concentrations in M. californianus are not likely to pose a risk for human health.