The Pacific geoduck Panopea generosa is distributed along the Pacific coast of the peninsula of Baja California, Mexico. Because of its high market value, this species has been under an intensive fishery pressure during the last few years, whereas its experimental aquaculture production is still developing. The fishery and culture practices point to the movement of clams as a risk factor for dispersion of symbionts, parasites, and diseases. Wild geoduck clams from fishery captures are sent to facilities that maintain clams alive, before marketing. Some of them show external abnormalities such as weakness and flaccidity, blisters, and darkening and thickening of the mantle surface and siphon. The objective of this study was to determinate if these abnormalities were related to parasites or diseases through conventional parasitological and histological analyses. The parasitological analysis showed two species of copepods, Pseudomyicola spinosus and a calanoid species in the mantle cavity and gills; additionally, a turbellarian species was also observed in the mantle cavity, none of these symbionts were related to tissue damage. The histological analysis showed that some weak-flaccid clams were in a postspawning condition. The dark and thick areas of the siphon and mantle suffered a dramatic transformation of the periostracum into a cavernous structure with numerous protozoans in different developmental stages. Fungi were occasionally observed in the external area of the periostracum. Unusual mortalities were reported by producers in clams with this abnormality. Rickettsia-like inclusions and trematodes were found in the digestive gland associated with limited damage to the host. The darkening and thickening of the siphon represent a major issue because of the negative appearance of the clams, which prevents its sale and is possibly related to the unusual mortality episodes. Detailed field and laboratory studies are needed to determine the origin of this pathology as well as its distribution and effect on the survival of the host. Moreover, field studies on the distribution, prevalence, and intensity of the other symbionts and parasites here detected are needed. These data constitute the first record for organisms associated with P. generosa in Mexico and a baseline for future studies.