INTRODUCTION: Due to high risk of septic transfusion reactions arising from bacterial contamination, US Food and Drug Administration regulations currently limit platelet storage to 5 days at room temperature (RT). However, blood culturing methods can take up to 7 days to detect bacteria, allowing transfusion of potentially contaminated units. Thus, cold storage (CS) may be a viable means of extending shelf life and improving safety. STUDY DESIGN AND METHODS: Platelets and fresh plasma (FP) were collected by apheresis from healthy donors, aliquoted, and challenged with Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, or Staphylococcus epidermidis. Aliquots were then stored at either RT or CS. RESULTS: Significant (p < 0.05) bacterial growth was detected at RT for most bacteria as early as Day 1 after collection, with peak growth occurring between Days 3 and 4. Growth remained static during CS. Additionally, platelets appeared to enhance bacterial replication with growth significantly lower (p < 0.05) in FP relative to RT-stored platelets. Lactic acid promoted bacterial growth when added to FP at RT. Bacterial challenge also resulted in significantly increased platelet activation (p < 0.05) and significantly reduced platelet function (p < 0.05) in RT storage relative to uninfected controls by Day 5 after collection. Conversely, CS ablated bacteria growth, limited platelet metabolism, and preserved platelet function throughout the study. CONCLUSION: These data suggest that CS presents an attractive alternative to RT to both extend storage life and reduce the risk of transfusion-related sepsis.