Background and purpose: People with multiple sclerosis (MS) suffer from higher infection‐related mortality compared to the general population; however, sparse data are available on the increased risk of death associated with coronavirus disease 2019 (COVID‐19) and other common types of infections. Methods: All mortality records and multiple‐cause‐of‐death data in 2010–2021 of residents in the Veneto region (northeastern Italy) were extracted. Mention of specific infections was compared between death certificates reporting MS or not. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated by conditional logistic regression matching by age, sex and calendar year. The bimonthly averages of MS‐related deaths in 2010–2019 were compared with those registered during the pandemic (2020–2021). Results: Of 580,015 deaths through 2010–2021, MS was mentioned in 850 cases (0.15%), 59.3% women. Influenza and pneumonia were reported in 18.4% of MS‐related compared to 11.0% non‐MS‐related deaths (OR 2.72, 95% CI 2.28–3.25). The odds of mention of urinary tract infections was significantly greater in MS‐related deaths of men (OR 8.16, 95% CI 5.23–12.7) than women (OR 3.03, 95% CI 1.82–5.02). Aspiration pneumonia, pressure ulcers/skin infections and sepsis were also significantly associated with MS‐related deaths. Reporting of COVID‐19 as a cause of death did not significantly differ between deaths with and without mention of MS (approximately 11% of both). However, compared to 2010–2019, peaks in MS‐related deaths were observed during the pandemic waves. Conclusions: Infections continue to play a significant role in MS‐related deaths, underlying the need to improve prevention and management strategies. [ABSTRACT FROM AUTHOR]