Perfluorinated compounds (PFCs) are globally distributed persistent environmental contaminants. This study provides temporal trends as well as large-scale spatial trends of PFC concentrations in threatened juvenile loggerhead sea turtles from Florida Bay, Florida, Cape Canaveral, Florida, Charleston, South Carolina, Core Sound, North Carolina, and Chesapeake Bay, Maryland. PFCs were extracted from 164 plasma and serum samples using solid-phase extraction and quantified with LC/MS/MS. Perfluorooctane sulfonate (PFOS) was the predominant compound detected in all loggerhead sea turtle samples (range 0.31 to 39.0 ng/g). Concentrations of six compounds significantly varied by location (p ≤ 0.01), with MD or FL Bay turtles having the highest PFC concentrations. FL turtles occupying inshore embayments had a higher proportion of perfluorocarboxylates compared to PFOS than other study sites. This study was the first to correlate wildlife PFC concentrations with human abundance; however, no significant correlation was found among study sites. PFOS and perfluorononanoate (PFNA) significantly decreased from 2000-2008 in the SC turtles (p ≤ 0.02) by 20% and 11%, respectively. PFOS and perfluorodecanoate (PFDA) were correlated to each other independent of region or year (r² ≥ 0.50). Future investigations should continue temporal assessments as PFC regulations change and attempt to pinpoint specific sources and transport pathways in areas with higher PFC contamination.