<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Diabetes mellitus worsens the prognosis of SARS‐CoV‐2 infection, and vaccination has been the major tool for reducing the risk of hospitalisation, and mortality.</jats:p><jats:p>The primary aim of this study was to evaluate the response to the SARS‐CoV‐2 vaccine in subjects with diabetes and controls. Differences between type 1 (T1D) and type 2 (T2D) diabetes and clinical determinants of vaccination response were also evaluated.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>128 subjects with diabetes (60 with T1D and 62 with T2D) and 202 subjects acting as controls who completed a full vaccination cycle with two doses of mRNA vaccine were enroled. People with previous SARS‐CoV‐2 infection were excluded. Antibodies (Ab) directed against the spike protein of the SARS‐CoV‐2 were evaluated at one and 6 months after vaccination.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the whole cohort, the Ab level was higher among women than in men (<jats:italic>p</jats:italic> = 0.011) and negatively correlated with age (rho = −0.155, <jats:italic>p</jats:italic> = 0.005). Subjects with diabetes showed decreased levels of Ab after one month compared to controls (1217[747–1887]BAU/mL vs. 1477[942–2556]BAU/mL, <jats:italic>p</jats:italic> = 0.002), even after correction for age and gender (<jats:italic>p</jats:italic> = 0.002). No difference was found between subjects with T1D and T2D. After 6 months, antibody levels significantly decreased in people with and without diabetes, with no differences between groups, although some subjects were lost at follow‐up. In subjects with diabetes, only a significant correlation was found between Ab level and renal function (rho 0.190, <jats:italic>p</jats:italic> = 0.042).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Both T1D and T2D are associated with a reduced early response to vaccination. The serum concentration of Ab significantly reduced over time in both groups, highlighting the relevance of vaccination boosters independently of the presence of diabetes.</jats:p></jats:sec>