Objectives: To determine the impact of the COVID-19 pandemic on the incidence rates of infection and islet autoimmunity in children at risk for type 1 diabetes. Methods: 1050 children aged 4 to 7 months with an elevated genetic risk for type 1 diabetes were recruited from Germany, Poland, Sweden, Belgium and the UK. Reported infection episodes and islet autoantibody development were monitored until age 40 months from February 2018 to February 2023. Results: The overall infection rate was 311 (95% Confidence Interval [CI], 304–318) per 100 person years. Infection rates differed by age, country, family history of type 1 diabetes, and period relative to the pandemic. Total infection rates were 321 per 100 person-years (95% CI 304–338) in the pre-pandemic period (until February 2020), 160 (95% CI 148–173) per 100 person-years in the first pandemic year (March 2020—February 2021; P < 0.001) and 337 (95% CI 315–363) per 100 person-years in subsequent years. Similar trends were observed for respiratory and gastrointestinal infections. Islet autoantibody incidence rates were 1.6 (95% CI 1.0–2.4) per 100 person-years in the pre-pandemic period, 1.2 (95% CI 0.8–1.9) per 100 person-years in the first pandemic year (P = 0.46), and 3.4 (95% CI 2.3–4.8) per 100 person-years in subsequent years (P = 0.005 vs. pre-pandemic year; P < 0.001 vs. first pandemic year). Conclusions: The COVID-19 pandemic was associated with significantly altered infection patterns. Islet autoantibody incidence rates increased two-fold when infection rates returned to pre-pandemic levels.