Vaccination is an effective way in providing protection against COVID-19 infection and severe outcomes. However, vaccine resistance and hesitancy are a great concern among vulnerable populations including older adults who live alone or only with an older partner. This study examined their vaccination status and reasons and associated factors of vaccine resistance and hesitancy. A cross-sectional study was conducted among older adults living alone or only with an older partner in communities in Hong Kong. Participants were interviewed between October 2021 and February 2022. Logistic regression analyses were employed to examine factors associated with vaccine resistance and hesitancy. Of the 2109 included participants, the mean age was 79.3 years (SD 7.6), 1460 (69.2%) were female, 1334 (63.3%) lived alone, and 1621 (76.9%) were receiving social security support. The vaccine uptake, non-uptake (i.e., resistance), and hesitancy rates were 50.1%, 34.4%, and 15.5%, respectively. The top four reasons for vaccine resistance and hesitancy were “Not feeling in good health” (27%), “Worry about vaccine side effects” (18%), “Feeling no need” (10%), and “Lack of recommendation from doctors” (9%). Vaccine resistance and hesitancy was significantly associated with older age, living alone, more chronic conditions, fewer types of social media use, and lower self-rated health status. Similar associations can be observed in their separate analysis for vaccine resistance and vaccine hesitancy, and ever hospital admission over the past 6 months was additionally related to vaccine hesitancy. Older people who live alone or only with an older partner had a low vaccination rate. Poor health or worry about vaccine side effects were the most common reasons for their vaccine resistance and hesitancy. Actions are greatly needed to improve the uptake rate among this vulnerable population, especially those who were older, have poorer health, and use less social media.