In this study, sugarcane juice subjected to both high-pressure processing (HPP) and thermal pasteurization (TP) was used to compare the changes in microbial levels, physicochemical properties, antioxidant capacity, sugar content, activity of sucrose neutral invertase, and sensory analysis during 28 days of refrigerated storage. Results showed that HPP treatment of 600 MPa and TP significantly reduced aerobic bacteria, coliform, and yeast counts. At day 28 of storage, HPP-treated juice (600 MPa/6 min) displayed no significant differences when compared to the fresh juice in terms of physicochemical properties such as total titratable acidity, pH, and total soluble solids. Although significant differences were observed in HPP-treated juice in color, antioxidants, and antioxidant capacity, the extent of the differences was substantially lower than that in thermal-treated juice, indicating that HPP treatment can retain better quality of sugarcane juice. After HPP treatment of 600 MPa and TP, invertase enzyme activity on day 7 declined to 87.69 and 82.86 %, respectively, which could possibly prevent sucrose conversion to fructose and glucose during refrigerated storage. Sensory testing showed no significant difference between HPP-treated juice and fresh juice, while TP reduced the acceptance of sugarcane juice. Collectively, this study indicated that HPP pasteurization can successfully reduce the microbial load in sugarcane juice. Meanwhile, HPP treatment maintains stable quality and inhibits enzyme activity, and thus, it can effectively extend shelf-life during refrigerated storage. Thus, HPP has a great potential in the development of drinks with fresh sugarcane juice.