This dataset uses the ITIS recommended Ortmanniana pectorosa, Conrad, 1834 in place of Actinonaias pectorosa, which was used in the Richard et al. 2020 manuscript. Biologists monitoring freshwater mussel (Order Unionida) populations rely on behavioral, often subjective, symptoms to identify “sick” or stressed animals, such as gaping valves and slow response to probing and lack clinical indicators to support a diagnosis. As part of a multi-year study to investigate causes of reoccurring mortality of pheasantshell (Ortmanniana pectorosa, Conrad 1834) in the Clinch River, Virginia and Tennessee, USA, we analyzed the hemolymph metabolome of a subset of mussels from the 2018 sampling period. Mussels at the mortality sites were diagnosed as affected (case) or unaffected (control) based on behavioral and physical signs. Hemolymph was collected in the field by nonlethal methods from the anterior adductor muscle for analysis. We used ultra-high-performance liquid chromatography, quadrupole time-of-flight mass spectroscopy (UHPLC-QTOF-MS) to detect targeted and untargeted metabolites in hemolymph and compared metabolomic profiles by field diagnosis. This dataset contains information about the viral load measured previously by Richard et al. 2020. We also include the intensity of mass spectrum signals from metabololites found in the hemolymph of pheasantshell mussels (Ortmanniana pectorosa, Conrad, 1834). These values are unitless values as the intensity is measured as the area under the curve for each metabolite.