Objective: This longitudinal study tested the relationship between cigarette and e-cigarette use and SARS-CoV-2 seroconversion among US college students. Participants: Undergraduate students (n = 764), drawn from a randomly selected invitation-only pool from a large Midwestern university, that were initially negative for SARS-CoV-2 antibodies and were re-tested in November were included in this study conducted in Fall 2020. Methods: Demographics and cigarette and e-cigarette use behaviors (nicotine use) were collected in a baseline survey. SARS-CoV-2 antibody tests were administered in September (baseline) and November (endline) of 2020. Log-binomial regression analyses were conducted to test the association between nicotine use and SARS-CoV-2 seroconversion. Results: SARS-CoV-2 seroconversion was 5.2%. No statistically significant associations were found between nicotine use and SARS-CoV-2 seroconversion. Conclusions: Contrary to prior results, we found no association between nicotine use and SARS-CoV-2 seroconversion. Nicotine use may not be a key risk factor for COVID-19 acquisition in predominantly healthy college-aged populations.