The Caribbean spiny lobster, Panulirus argus (Latreille, 1804) is a highly commercial species and comprises the largest spiny lobster fishery in the world. Although populations have declined throughout its range, there is little known regarding its diseases and pathogens. The objectives of this study were to provide illustrated and standardized methods for postmortem examination, and to describe baseline gross and microscopic pathology for P. argus. From July 2017–March 2019, a postmortem examination including comprehensive histological assessment was performed on 313 fishery-caught lobsters. Epibionts and lesions observed include branchial cirriped infestation (69%), branchial encysted nemertean worm larvae (23%), tail fan necrosis (11%), skeletal muscle necrosis (7%), antennal gland calculi (6%), branchial infarction (2%), and microsporidiosis (0.6%). This report confirms the rare prevalence of microsporidiosis in P. argus and describes nemertean worm larvae in the gill. This study also reports a condition resembling excretory calcinosis in spiny lobster. The methods and data produced by this study facilitate disease diagnosis and sustainable stock management of P. argus.