This study examined the prevalence of mental health concerns and its association with COVID-19, selected social determinants of health, and psychosocial risk factors in a predominantly racial/ethnic minoritized neighborhood in New York City. Adult Harlem residents (N = 393) completed an online cross-sectional survey from April to September 2021. The Patient Health Questionnaire (PHQ-4) and the Post-Traumatic Stress Disorder (PC-PTSD) were used to evaluate mental health concerns. Poisson regression with robust variance quantified the associations of interests via prevalence ratios (PR) and 95% confidence intervals (CI). Two-thirds (66.4%) of theresidents reported experiencing mental health concerns, including PTSD (25.7%), depression (41.2%), and anxiety (48.1%). Residents with low-income housing status (PR = 1.16; 95% CI 1.01, 1.34), alcohol misuse (PR = 1.68; 95% CI 1.40, 2.01), food insecurity (PR = 1.23; 95% CI 1.07, 1.42), exposure to interpersonal violence (PR = 1.33; 95% CI 1.08, 2.65), and experience of discrimination (PR = 1.53, 95% CI 1.23-1.92) were more likely to report mental health concerns. Better community perception of the police (PR = 0.97, 95% CI 0.95, 0.99) was associated with fewer mental health concerns. No associations were observed for employment insecurity, housing insecurity, or household COVID-19 positivity with mental health concerns. This study showed a high prevalence of mental health concerns in a low-income racial/ethnic minoritized community, where COVID-19 and social risk factors compounded these concerns. Harlem residents face mental health risks including increased financial precarity, interpersonal violence, and discrimination exposure. Interventions are needed to address these concurrent mental health and psychosocial risk factors, particularly in racial/ethnic minoritized residents.