Introduction <p>The COVID-19 pandemic had profound effects for both infected and uninfected individuals. We aimed to identify acute and chronic epigenetic alterations from SARS-CoV-2 infection and/or lockdown measures.</p> Methods <p>Both infected and uninfected participants from the TwinsUK cohort (<i>n</i> = 139) provided longitudinal whole-blood samples (Spring 2020, Spring 2021). Cross-sectional and longitudinal DNA methylome [DNAm] changes, including epigenetic ageing clocks, were assessed, and EWAS (Epigenome-Wide Association Studies) were performed. Changes in epigenetic ageing clocks were compared with longitudinal samples from an independent pre-pandemic cohort (<i>n</i> = 35, Nurses’ Health Study II cohort), assessed similarly.</p> Results <p>Irrespective of SARS-CoV-2 infection, all individuals exhibited accelerated ageing from 2020 to 2021 (GrimAge clock age acceleration: p-value = 0.002, β = 0.99). In contrast, epigenetic data from paired samples from a separate pre-pandemic cohort, over a similar time period and assessed similarly, did not exhibit GrimAge acceleration. Epigenetic ageing did not differ between infected and uninfected individuals, or between recent and distant SARS-CoV-2 infection. Lastly, EWAS identified several putative changes in DNAm associated with recent, and distant, SARS-CoV-2 infection.</p> Conclusions <p>Our longitudinal results suggest that the pandemic accelerated epigenetic ageing rates, irrespective of recent or distant SARS-CoV-2 infection.</p>