The outbreak of coronavirus disease (COVID-19) has severely affected the global and Uganda economy with major victims being small, and medium-sized enterprises (SMEs). The study examined the organizational preparedness and business disaster of SMEs during COVID-19 pandemic in Kigezi sub-region in South Western Uganda. The specific objectives were to (i) determine the characteristics of decision makers of SMEs during the COVID-19 pandemics; (ii) assess organizational features of SMEs during the COVID-19 pandemics; and (iii) examine government response and preparedness of SMEs during the COVID-19 pandemics. A cross sectional survey research design was employed and interviewer-administered questionnaire as research tool was used to elicit information from the managers of SMEs across the six (6) districts of Kigezi sub-region. Two-stage cluster sampling technique was used and the sample size was computed using Yamane’s sampling formulae based on a 5% level of precision. The value of CVI obtained was 0.840 while the value of reliability obtained was 0.770, which indicates that the questionnaire items were relevant and suitable for the study. Five hundred and ninety-one (591) questionnaires were administered to the SMEs owners/managers while four hundred and seventy-six (476) questionnaires were returned giving the overall return rate as 81%. The study identifies the factors who were significant with organizational preparedness and the management of business during COVID-19 pandemics in Kigezi sub-region in South Western Uganda as firm size, firm financial condition, risk perception, government subsidy, help received from NGOs and the loan received from the bank/SACCO while other factors: firm year of existence, source of initial capital, and gender of owners/managers were found to be insignificant. The study concludes that organization features and characteristics of decision makers are important factors that affect the organizational preparedness and the management of business during COVID-19 pandemics in Kigezi sub-region in South Western Uganda. The study recommends that SMEs owners/managers should focus on improving their firms’ features; perfect the way they make decision by providing a critical dynamic resilience strategy framework to manage their SMEs during the crisis period.