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We explored whether influenza vaccination (IV) affects susceptibility to SARS-CoV-2 infection and clinical outcomes in COVID-19 patients in 17,608 residents of the Italian province of Reggio Emilia undergoing a SARS-CoV-2 test. Exposure to IV was ascertained and the strength of the association with SARS-CoV-2 positivity expressed with odds ratios (OR). Rates of hospitalisations and death in those found positive were assessed and hazard ratios (HR) were estimated. The prevalence of IV was 34.3% in the 4885 SARS-CoV-2 positive and 29.5% in the 12,723 negative subjects, but the adjusted OR indicated that vaccinated individuals had a lower probability of testing positive (OR = 0.89; 95% CI 0.80–0.99). Among the 4885 positive individuals, 1676 had received IV. After adjusting for confounding factors, there was no association between IV and hospitalisation (1.00; 95% CI 0.84–1.29) or death (HR = 1.14; 95% CI 0.95–1.37). However, for patients age ≥65 vaccinated close to the SARS-CoV-2 outbreak, HRs were 0.66 (95% CI: 0.44–0.98) and 0.70 (95% CI 0.50–1.00), for hospitalisation and death, respectively. In this study, IV was associated with a lower probability of COVID-19 diagnosis. In COVID-19 patients, overall, IV did not affect outcomes, although a protective effect was observed for the elderly receiving IV almost in parallel with the SARS-CoV-2 outbreak. These findings provide reassurance in planning IV campaigns and underscore the need for exploring further their impact on COVID-19.