Red Snapper (Lutjanus campechanus) were collected throughout the Gulf of Mexico (GoM) from 2011 to 2017 and analyzed for biliary (n = 496) fluorescent aromatic compounds (FACs), hepatic (n = 297) polycyclic aromatic hydrocarbons (PAHs) and microscopic hepatobiliary changes (MHC, n = 152). Gross and histological evaluations were conducted with liver tissues to identify and characterize pathological changes. This is the first report to interrelate hepatobiliary PAH concentrations and MHCs in Red Snapper. Hepatic PAHs measured in GoM Red Snapper ranged from 192 to 8530 ng g−1 w.w. and biliary FACs ranged from 480 to 1,100,000 ng FAC g−1 bile. Biliary FACs in Red Snapper collected along the west Florida Shelf and north central region declined after 2011 and were relatively stable until a sharp increase was noted in 2017. Increases in the PAH exposures are likely due to a number of sources including leaking infrastructure, annual spills, riverine input and the resuspension of contaminated sediments. In contrast, hepatic PAH concentrations were relatively stable indicating Red Snapper are able to maintain metabolic clearance however this energetic cost may be manifesting as microscopic hepatic changes (MHCs). Virtually all (99 %) of the evaluated Red Snapper had one to nine MHCs with an average of five coinciding changes in an individual fish. The observed changes were broadly classified as inflammatory responses, metabolic responses, degenerative lesions, nonneoplastic proliferation and neoplastic lesions. Biliary FACs were associated with parasitic infection and intracellular breakdown product accumulation such as intra-macrophage hemosiderin, lipofuscin and ceroid laden prevalence. Whereas, hepatic PAHs were associated with increased myxozoan plasmodia prevalence. This study evaluates relationships between hepatobiliary PAH concentrations and biometrics, somatic indices, condition factors and microscopic hepatic changes in Red Snapper located in the north central GoM. Together, these results may be signaling increased disease progression in Gulf of Mexico Red Snapper more than likely resulting from chronic environmental stressors including elevated PAH exposures and concentrations.