Platelet granules contain a diverse group of proteins. Upon activation and during storage, platelets release a number of proteins into the circulation or supernatant of stored platelet concentrate (PC). The aim of this work was to investigate the effect of pathogen inactivation (PI) on a selection of proteins released in stored platelets. Materials and Methods: PCs in platelet additive solution (PAS) were produced from whole blood donations using the buffy coat (BC) method. PCs in the treatment arm were pathogen inactivated with amotosalen and UVA, while PCs in the second arm were used as an untreated platelet control. Concentrations of 36 proteins were monitored in the PCs during storage. Results: The majority of proteins increased in concentration over the storage period. In addition, 10 of the 29 proteins that showed change had significantly different concentrations between the PI treatment and the control at one or more timepoints. A subset of six proteins displayed a PI-related drop in concentration. Conclusions: PI has limited effect on protein concentration stored PC supernatant. The protein’s changes related to PI treatment with elevated concentration implicate accelerated Platelet storage lesion (PSL); in contrast, there are potential novel benefits to PI related decrease in protein concentration that need further investigation.