PFAAs (Perfluoroalkyl acids) are a class of bioaccumulative, persistent and ubiquitous aquatic contaminants. A paucity of toxicological information exists for short chain PFAAs and PFAA mixtures. In order to address these knowledge gaps, we performed a 3-week, aqueous exposure of rainbow trout to 3 different concentrations of a PFAA mixture (50 - 500 ng/L) and individual PFAAs (25 nM of PFOS, PFOA, PFBS or PFBA). Untargeted proteomics and were conducted on the blood plasma and head kidney tissue to evaluate differences in biological effect for congeners and mixtures. The mixture and PFOS exposures significantly altered the abundances of many plasma proteins involved in lipid metabolism and the nervous system. The PFOA and high mixture treatments altered many kidney proteins involved in oxidative stress and inflammation. The findings emphasize the need for more toxicological testing of PFAA mixtures and their potential to cause metabolic dysregulation and neurotoxicity in fish.