Social isolation is associated with decreased intent to receive vaccination against coronavirus disease 2019 (COVID-19); however, its association with COVID-19 vaccine uptake is unknown. The present study aimed to determine the association between social isolation and subsequent COVID-19 vaccination using the data from a representative Japanese sample. Longitudinal observational study. Japanese citizens aged ≥ 65years who participated in the Quality of Life in COVID-19 Era (QoLCoVE) study which began in March 2020. Social isolation was assessed in March 2020 using the abbreviated Lubben Social Network Scale, with a score of ≤ 11 indicating social isolation. To evaluate the relationship between social isolation at the baseline and COVID-19 vaccine uptake (including reservation for vaccine administration) between August and September 2021, we estimated adjusted risk ratios with 95% CIs using modified Poisson regression with adjustment for potential confounders. A total of 921 participants met the inclusion criteria in the initial survey, of whom 720 (78.2%) completed the follow-up survey. Median age was 70years (interquartile range: 66-72), and 329 (45.7%) participants were male. Twenty-one (16.5%) of 127 socially isolated participants, and 48 (8.1%) of 593 non-socially isolated participants did not receive the COVID-19 vaccine. Socially isolated participants were less likely to take COVID-19 vaccine than non-socially isolated participants (adjusted risk ratio 1.98, 95% CI: 1.18-3.32). Social isolation is associated with reduced COVID-19 vaccine uptake among older adults. To further promote COVID-19 vaccination in the older population, support for social isolation might be necessary.