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Background: Cardiovascular implantable electronic device (CIED) infections are a common indication for device extraction. Early diagnosis and complete system removal are crucial to reduce morbidity and mortality. The lack of clear infectious symptoms makes the diagnosis of pocket infections challenging and may delay referral for extraction., Objective: We aimed to determine if inflammatory biomarkers can help diagnose CIED isolated pocket infection., Methods: We performed a retrospective analysis of all patients undergoing transvenous lead extraction for CIED infection at the University of California San Diego from 2012 to 2022 (N = 156). Patients were classified as systemic infection (n = 88) or isolated pocket infection (n = 68). Prospectively collected preoperative procalcitonin (PCT), C-reactive protein, and white blood cell count were compared between groups., Results: Pairwise comparisons revealed that the systemic infection group had a higher PCT than the control group ( P < .001) and the pocket infection group ( P = .009). However, there was no significant difference in PCT value between control subjects and isolated pocket infection subjects. Higher white blood cell count was only associated with systemic infection when compared with our control group ( P = .018)., Conclusion: In patients diagnosed with CIED infections requiring extraction, inflammatory biomarkers were not elevated in isolated pocket infection. Inflammatory markers are not predictive of the diagnosis of pocket infections, which ultimately requires a high level of clinical suspicion., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)