Despite the availability of effective treatments, Sarcoptes scabiei remains a major health problem in the pig industry. Unsuccessful control of the disease is often due to the lack of reliable detection methods, with current tests relying on skin scrapings and crude antigen ELISAs. A previous analysis of antigens in pig skin scrapings reported that anti-transferrin antibodies were present in S. scabiei infected animals and that this finding might be considered as a useful diagnostic tool. This paper confirms IgG autoantibodies against transferrin, including the first report of IgM autoantibodies, in both naturally and experimentally infected pigs using ELISA and dot blot assays. Autoantibodies were also detected in pigs to ferritin and to a lesser extent lactoferrin. Immunoblotting confirmed the presence of IgG and IgM autoantibodies in mange positive pigs, as well as IgM antibodies to transferrin and albumin in mange negative pigs. These findings suggest the presence of natural autoantibodies to transferrin and albumin in pigs. The development of the IgG autoimmune response may either be a host mechanism for limiting iron to the mite via antibody mediated clearance, the result of host exposure to mite iron-binding homologues or because of a mite-induced antigenic change to host transferrin. Further investigation into the formation of these autoantibodies may provide insights into the importance of iron in scabies infections and the development and perseverance of S. scabiei infections in pigs. The specificity and sensitivity of the anti-transferrin response reinforces its potential in the diagnosis of scabies in pigs.