Forced quarantine and nationwide lockdowns have been a primary response by many jurisdictions in their attempt at COVID-19 elimination or containment, yet the associated mental health burden is not fully understood. Using an eight country cross-sectional design, this study investigates the association between COVID-19 induced quarantine and/or isolation on probable generalized anxiety disorder (GAD) and major depressive episode (MDE) psychological outcomes approximately eight months after the pandemic was declared. Overall, 9027 adults participated, and 2937 (32.5%) were indicated with GAD and/or MDE. Reported quarantine and/or isolation was common, with 1199 (13.8%) confined for travel or health requirements, 566 (6.5%) for being close contact, 720 (8.3%) for having COVID-19 symptoms, and 457 (5.3%) for being COVID-19 positive. Compared to those not quarantining or isolating, the adjusted estimated relative risks of GAD and/or MDE associated with quarantine and/or isolation was significant (p < 0.001), ranging from 1.24 (95% confidence interval [CI]: 1.07, 1.43) for travel/health to 1.37 (95% CI 1.19, 1.59) for COVID-19 symptom isolation reasons. While almost universally employed, quarantine and/or isolation is associated with a heavy mental health toll. Preventive strategies are needed, such as minimizing time-limits imposed and providing clear rationale and information, together with additional treatment and rehabilitation resources. [ABSTRACT FROM AUTHOR]