Background: Cigarette smoking results in altered immune cell function and associated systemic inflammation, as observed in chronic obstructive pulmonary disease (COPD). Electronic (e-) cigarettes are novel, popular tobacco products frequently advertised as a safer alternative to traditional cigarettes; however, the effects of their regular use on immune cell function are currently unknown. Thus, the purpose of this study was to investigate the impact of e-cigarette usage and the role of nicotine on the immune cell profile of young, regular users. Methods: Twenty-five young, apparently healthy, regular users of e-cigarettes (EU, age: 23±3 y.) and twenty-two non-users (NU, age: 23±4 y.) participated in this study. A fasted venous blood sample was obtained from all participants for a complete blood count and nicotine concentrations. EU were randomized to either nicotine or nicotine-free products for fourteen days and completed a second assessment to investigate changes in the immune cell profile based on either increased (+C; n=11) or decreased (-C; n=9) nicotine usage accessed via cotinine levels. For comparison, the same assessments were completed in a group of 13 patients with a diagnosis of COPD (67±9 y., GOLD Stage II-IV). Results: Regular users of e-cigarettes exhibit significantly higher eosinophils (absolute, p=0.008, percentage, p=0.042) and platelets ( p=0.018) when compared to non-users but similar ( p≥0.431) to patients with COPD. White blood cell, neutrophil, monocyte, and lymphocyte counts were similar between the EU and NU. After fourteen days, despite significant changes in nicotine (Δ+C=+2±4 vs. Δ-C=-3±4 ng/mL, p=0.014) and cotinine (Δ+C=+28±27 vs. Δ-C=-141±120 ng/mL, p=0.001) between +C and -C groups, no differences in the immune cell profiles were observed. To note, no association between immune cells and nicotine levels at baseline or follow-up (nicotine: r≤0.352; p≥0.122; cotinine: r≤0.310; p≥0.126). Conclusions: Results of the study suggests that regular users of e-cigarettes present with altered immune cell profile in eosinophils and platelets when compared to non-users. The elevated immune cell markers were comparable to observed values in patients with COPD and have been associated with adverse effects on pulmonary and cardiovascular health. In addition, the elevated immune cell profile was not related to changes in nicotine, inferring that other e-liquid components may have an effect on innate immunity. Future studies are warranted to investigate the long-term effects of e-cigarette use and their components on immune cell profile. Supported in part by a Rapid Response Project NIDA/FDA (PRM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.