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Background: The South Asian Association for Regional Cooperation (SAARC) covers Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. We conducted a comparative analysis of the trade-off between the health policies for the prevention of COVID-19 spread and the impact of these policies on the economies and livelihoods of the South Asia populations., Methods: We analyzed COVID-19 data on epidemiology, public health and health policy, health system capacity, and macroeconomic indicators from January 2020 to March 2021 to determine temporal trends by conducting joinpoint regression analysis using average weekly percent change (AWPC)., Results: Bangladesh had the highest statistically significant AWPC for new COVID-19 cases (17.0; 95% CI = 7.7-27.1, P < 0.001), followed by the Maldives (12.9; 95% CI = 5.3-21.0, P < 0.001) and India (10.0; 95% CI = 8.4-11.5, P < 0.001). The AWPC for COVID-19 deaths was significant for India (6.5; 95% CI = 4.3-8.9, P < 0.001) and Bangladesh (6.1; 95% CI = 3.7-8.5, P < 0.001). Nepal (55.79%), and India (34.91%) had the second- and third-highest increase in unemployment, while Afghanistan (6.83%) and Pakistan (16.83%) had the lowest. The rate of change of real GDP had the highest decrease for Maldives (557.51%), and India (297.03%); Pakistan (46.46%) and Bangladesh (70.80%), however, had the lowest decrease. The government response stringency index for Pakistan had a see-saw pattern with a sharp decline followed by an increase in the government health policy restrictions that approximated the test-positivity trend., Conclusions: Unlike developed economies, the South Asian developing countries experienced a trade-off between health policy and their economies during the COVID-19 pandemic. South Asian countries (Nepal and India), with extended periods of lockdowns and a mismatch between temporal trends of government response stringency index and the test-positivity or disease incidence, had higher adverse economic effects, unemployment, and burden of COVID-19. Pakistan demonstrated targeted lockdowns with a rapid see-saw pattern of government health policy response that approximated the test-positivity trend and resulted in lesser adverse economic effects, unemployment, and burden of COVID-19., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose the following activities and/or relationships: FBI reports grant from NorthStar Anesthesia, and personal fees for consultancy from Silicon Valley Innovation Center, Infineon Technologies AG, unrelated to this publication. All other authors declare no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)