Autoimmune diseases develop due to the interaction between genetic susceptibility and additional factors, such as environmental exposure to toxicants. Mercury (Hg), a well-established neurotoxin, has more recently been studied as an immunotoxin linked with biomarkers of autoimmunity, including the presence of antinuclear antibodies (ANA) and distinct cytokine profiles. Mercury (Hg) is virtually ubiquitous in the environment, and concerns about the potential health impacts of Hg exposure through fish consumption exist. Few studies have specifically examined the relationships among mercury, fish consumption, and autoimmune biomarkers in human populations. The findings of these studies are conflicting; this may be due to confounding exposures and opposing mechanisms of action. Additional studies are necessary to clarify the role of Hg through seafood consumption in autoimmunity.