The study developed a model for organizational preparedness and business disaster of SMEs in Kigezi sub-region in South Western Uganda. 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 results showed that organization features, characteristics of decision makers and government response accounts for a total of 27.9% improvement on the management of business disaster in Kigezi sub-region. The results further indicate that organization features (β= 0.163, p-value=0.000) and characteristics of decision makers (β= 0.021, pvalue=0.648) have positive but significant effect while government response (β= -0.780, p-value=0.682) has negative but no significant effect on the management of business disaster. 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 there is a need for government/NGOs interventions in the area of subsidy for SMEs owners/managers during the pandemic to boost their businesses.