In 2022, the Shanghai municipal government enforced strict COVID-19 lockdown measures. Lockdown experiences for college students varied. Local students normally returned home and had familial support while non-local students relied more on institutional support when quarantining in dormitories. The difference could profoundly impact their access to necessary material resources and emotional support, affecting their mental health. This study compared the psychological effects of the Shanghai Lockdown on local and non-local college students using an explanatory-sequential mixed methods design. Quantitative analyses of data from 327 college students examined local and non-local students' mental health outcomes during the lockdown. Follow-up qualitative interviews (N = 12) contextualized their sources of stress and group differences. Higher prevalences of probable anxiety (34.6%), depression (45.1%), and poor subjective mental well-being (65.4%) are found among non-local students compared to local students (23.7% anxiety, 29.4% depressive symptoms, and 47.9% poor well-being). Suicidal ideation was higher among local students (8.6% prevalence difference). Being a non-local college student was associated with increased odds of probable anxiety, depression, and poor well-being. Interviews identified group differences such that non-local students received more school support (i.e., food and financial) and perceived emotional support but faced poorer quarantine living environments compared to local peers. Non-local college students were more vulnerable to the impact of lockdown. Our findings also provide insights into the impact of familial versus institutional support on student mental health during times of crisis.