The aim of this study was to test the hypothesis that Puffy Skin Disease (PSD) has an infectious aetiology, by undertaking a cohabitation experiment whereby naive triploid and diploid rainbow trout were cohabited with PSD-affected fish collected from the field. In addition, extensive additional investigations, including analysis of high-throughput sequencing datasets generated from skin samples of PSD-affected fish were undertaken in an attempt to identify potential infectious agents that may be responsible for PSD.