. Significance: The combination of polarized imaging with artificial intelligence (AI) technology has provided a powerful tool for performing an objective and precise diagnosis in medicine. Aim: An approach is proposed for the detection of hepatitis B (HB) virus using a combined Mueller matrix imaging technique and deep learning method. Approach: In the proposed approach, Mueller matrix imaging polarimetry is applied to obtain Mueller matrix images of 138 HBsAg-containing (positive) serum samples and 136 HBsAg-free (negative) serum samples. The kernel estimation density results show that, of the 16 Mueller matrix elements, elements and provide the best discriminatory power between the positive and negative samples. Results: As a result, and are taken as the inputs to five different deep learning models: Xception, VGG16, VGG19, ResNet 50, and ResNet150. It is shown that the optimal classification accuracy (94.5%) is obtained using the VGG19 model with element as the input. Conclusions: Overall, the results confirm that the proposed hybrid Mueller matrix imaging and AI framework provides a simple and effective approach for HB virus detection.