Objective To examine the epidemiology of sense of alienation (SoA) and its associations with depressive symptoms and poor sleep quality (PSQ) in Chinese older adults who experienced lockdown during the COVID-19 pandemic. Background There is a dearth of data on SoA in older adults during the COVID-19 pandemic. Methods Altogether, 543 community-dwelling older adults (50+ years) were recruited via the three-tier mental health network in Wuhan, China, and completed an online questionnaire in April 2020, the first month after the reopening of Wuhan. SoA, depressive symptoms, and sleep quality were measured by using the General Social Alienation Scale, Depression Anxiety and Stress Scale, and a single standardized question, respectively. Results The prevalence of SoA was 52.3% (95% confidence interval: 48.1–56.5%). Factors associated with higher levels of SoA were religious belief (β = 1.960, P = .024), monthly family income<4000 RMB (β = 1.405, P = .022), unemployment (β = 1.217, P = .039), fair or poor physical health (β = 2.202, P = .002), never and sometimes receiving community support (β = 2.297, P < .001 and β = 3.417, P < .001), perceiving a low possibility of a cure for COVID-19 (β = 2.379, P < .001), and affirmative and unsure fear of COVID-19 patients (β = 2.025, P = .007 and β = 1.101, P = .027). After adjusting for sociodemographic and pandemic-related variables, a one-SD increment in the SoA score was significantly associated with depressive symptoms (Odd Ratio [OR] = 5.59, P < .001) and poor sleep quality (Odd Ratio = 2.00, P < .001). Conclusion Over half of the older adults who experienced lockdown felt alienated, and SoA was independently associated with their depressive symptoms and PSQ. Efforts are warranted to address SoA in older adults who experienced lockdown during the pandemic.