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The COVID-19 pandemic has affected job satisfaction among healthcare workers; yet this has not been empirically examined in sub-Saharan Africa (SSA). We addressed this gap by examining job satisfaction and associated factors among healthcare workers in Ghana and Kenya during the COVID-19 pandemic. We conducted a cross-sectional study with healthcare workers (N = 1012). The two phased data collection included: (1) survey data collected in Ghana from April 17 to May 31, 2020, and (2) survey data collected in Ghana and Kenya from November 9, 2020, to March 8, 2021. We utilized a quantitative measure of job satisfaction, as well as validated psychosocial measures of perceived preparedness, stress, and burnout; and conducted descriptive, bivariable, and multivariable analysis using ordered logistic regression. We found high levels of job dissatisfaction (38.1%), low perceived preparedness (62.2%), stress (70.5%), and burnout (69.4%) among providers. High perceived preparedness was positively associated with higher job satisfaction (adjusted proportional odds ratio (APOR) = 2.83, CI [1.66,4.84]); while high stress and burnout were associated with lower job satisfaction (APOR = 0.18, CI [0.09,0.37] and APOR = 0.38, CI [0.252,0.583] for high stress and burnout respectively). Other factors positively associated with job satisfaction included prior job satisfaction, perceived appreciation from management, and perceived communication from management. Fear of infection was negatively associated with job satisfaction. The COVID-19 pandemic has negatively impacted job satisfaction among healthcare workers. Inadequate preparedness, stress, and burnout are significant contributing factors. Given the already strained healthcare system and low morale among healthcare workers in SSA, efforts are needed to increase preparedness, better manage stress and burnout, and improve job satisfaction, especially during the pandemic.