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Background: The COVID-19 pandemic is an unprecedented stressor for frontline healthcare workers, notably increasing acute stress disorder and depression rates. Emotion regulation and social support could be major protective factors against such psychopathological states, but their role has not been explored outside Western contexts. Objective: To assess the association between emotion regulation, social support, acute stress disorder, and depression among healthcare workers directly confronted with the first wave of COVID-19 pandemic in the eastern Democratic Republic of the Congo. Method: A cross-sectional study assessed acute stress disorder, depression, adaptive (i.e. acceptance, positive refocusing, ...) and maladaptive (i.e. self-blame, rumination, catastrophizing, ...) emotion regulation strategies, social support (instrumental, emotional, and informational levels), as well as self-reported situations and feelings related to COVID-19, in a population of 252 frontline healthcare workers (121 women; 131 men; mean age: 39 ± 11 years old) at the Referral General Hospital of Bukavu. We also explored the relations between these variables through bivariate and multivariate logistic regression. Results: Forty percent of participants presented symptoms of depression, and 16% presented acute stress disorder. In bivariate logistic regression, these psychiatric outcomes were associated with the availability of a COVID-19 protection kit [OR = 0.24 (0.12–0.98)], hostility toward health workers [OR = 3.21 (1.23–4.21)], putting into perspective [OR = 0.91 (0.43–0.98)], self-blame [OR = 1.44 (1.11–2.39)], catastrophizing [OR = 1.85 (1.01–4.28)], blaming others [OR = 1.77 (1.04–3.32)], emotional support [OR = 0.83 (0.49–0.98)], instrumental support [OR = 0.74 (0.28–0.94)], and informational support [OR = 0.73 (0.43–0.98)]. In multivariate logistic regression, hostility [OR = 2.21 (1.54–3.78)], self-blame [OR = 1.57 (1.02-2.11)], rumination [OR = 1.49 (1.11-3.13)] and emotional support [OR = 0.94 (0.65-0.98)] remained significantly associated with psychiatric outcomes. Conclusion: Depression and acute stress disorder were highly prevalent among Congolese healthcare workers during the first wave of the COVID-19 health pandemic. Hostility, self-blame, rumination, and social support were associated with depression and/or acute stress disorder and should be targeted by interventions aiming to support health workers' wellbeing. Frontline health workers presented high prevalence of acute stress disorder (16%) and depression (40%) during the first wave of COVID-19 pandemic in the Eastern Democratic Republic of the Congo, as they were working in hostile environment without enough protection kits. Acute stress disorder and depression were negatively associated with adaptive emotion regulation and social support; and positively with maladaptive emotion regulation. Intervention aiming to support health workers in pandemics should target emotion regulation and social support. [ABSTRACT FROM AUTHOR]