Sea star wasting disease (SSWD) is a suite of poorly described non-specific clinical signs including abnormal posture, epidermal ulceration, and limb autotomy (sloughing) causing mortalities of over 20 species of sea stars and subsequent ecological shifts throughout the northeastern Pacific. While SSWD is widely assumed to be infectious with environmental conditions facilitating disease progression, little data exist on cellular changes associated with disease that could inform mechanisms of disease pathogenesis and host susceptibility. Here, we replicated SSWD by exposing captive Pisaster ochraceus to a suite of non-infectious organic substances and show that development of gross lesions is a basal to surface process involving inflammation (e.g. infiltration of coelomocytes) of ossicles and mutable collagenous tissues leading to epidermal ulceration. Affected sea stars also manifest increases in a heretofore undocumented coelomocyte type, spindle cells, that might be a useful marker of inflammation in this species. Finally, compared to purple morphs, orange P. ochraceus developed more severe lesions and survived longer. Longer lived, and presumably more visible severely lesioned orange sea stars, could have important demographic implications in terms of detectability of lesioned animals in the wild and measures of apparent prevalence of disease.