Background: The incidence of infective endocarditis (IE) has increased in recent decades. Societal lockdown including reorganization of the healthcare system during the COVID-19 pandemic may influence the incidence of IE. This study sets out to investigate the incidence of IE during the Danish national lockdown. Methods: In this nationwide cohort study, patients admitted with IE in either one of two periods A) A combined period of 1 January to 7 May for 2018 and 2019, or B) 1 January to 6 May 2020, were identified using Danish nationwide registries. Weekly incidence rates of IE admissions for the 2018/2019-period and 2020-period were computed and incidence rate ratios (IRR) for 2020-incidence vs 2018/2019-incidence were calculated using Poisson regression analysis. Results: In total, 208 (67.3% men, median age 74.1 years) and 429 (64.1% men, median age 72.7 years) patients were admitted with IE in 2020 and 2018/2019, respectively. No significant difference in incidence rates were found comparing the 2020-period and 2018/2019-period (IRR: 0.96 (95% CI: 0.82–1.14). The overall incidence rate pre-lockdown (week 1–10: 1 January to 11 March 2020) was 14.2 IE cases per 100,000 person years (95% CI: 12.0–16.9) as compared with 11.4 IE cases per 100,000 person years (95% CI: 9.1–14.1) during lockdown (week 11–18: 12 March to 6 May 2020) corresponding to an IRR of 0.80 (95% CI: 0.60–1.06) and thus no significant difference pre- versus post-lockdown. Conclusion: In this nationwide cohort study, no significant difference in the incidence of IE admissions during the national lockdown due to the COVID-19 pandemic was found.