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The study is conducted to determine the factors that affect the level of information sharing between supply chain partners. 157 SMEs in the Mekong Delta were interviewed by using convenience sampling method. The Cronbach-s Alpha, exploratory factor analysis, multiple regression and discriminant analysis methods were used in this research. The result showed that information sharing was positively influenced by 7 factors: firm size, IT enablers, top management, trust in supply chain partners, commitment of supply chain partners, shared vision between supply chain partners and technology uncertainty; but negatively affected by customer uncertainty. Information sharing between supply chain partners is not impacted by supplier uncertainty. The result also indicated that IT enablers, technology uncertainty and commitment of supply chain partners were the three most important factors in discriminating between the organizations with high levels of information sharing and those with low levels of information sharing. Moreover, the levels of information sharing are depended on the organizational characteristics (types, operation years, total assets and number of employees). Finally, the paper has contributed on literature review and practical application in the case of SMEs in Vietnam.