The New Zealand Greenshell™ mussel (Perna canaliculus) is endemic to New Zealand and contributes to the success of the country’s aquaculture industry. However, summer mortality and potential disease outbreak events are having an increasing effect on the growth of this industry. The cause of these mortalities remains unknown, and histopathological studies of the pathogen and parasites in mussels are still incomplete. In the present study, a histological approach was used to identify pathogens and parasites, as well as immunological tissue responses in unhealthy- and healthy-looking P. canaliculus during a summer mortality event in 2018. A highly significant association between health conditions and the presence of Perkinsus olseni in mussels was observed. A higher prevalence of P. olseni, Apicomplexan-X (APX), and bacterial (rods and cocci) infections were noted in the unhealthy-looking mussels than in the healthy-looking mussels. In an assessment of stains, hematoxylin and eosin (H&E) staining appeared to be the best method for general pathological and anatomical characterization, while Giemsa provided the clearest visual definition of bacteria. In this aspect, it was comparable to Ziehl–Neelsen (ZN) in apparent sensitivity. Although Gram and ZN staining revealed bacterial cells marginally better than with H&E, their differential staining could not be assessed as no Gram-positive or acid-fast bacteria were seen, and no mussel-positive controls were available for comparison. This study also provides an illustrated guide to some significant mussel health indicators.