In this study, the isotopic composition (δ13C and δ15N), total organic carbon content, total nitrogen content, and C/N ratios of suspended particulate organic matter (POM) in Zhanjiang Bay, which is a semi-enclosed bay with concentrated artificial activities in Southern China, were analyzed in order to investigate the seasonal variations in the principal POM sources in the monsoon region. In summer, the δ13C and δ15N values showed a weak correlation with the chlorophyll a (Chl a), suggesting that terrigenous sources were dominant. However, in winter, the particulate organic carbon and particulate nitrogen values were correlated with the Chl a in the middle bay and bay mouth. Moreover, the δ13C values showed a significant correlation with Chl a during the winter, indicating that the contribution of the in situ phytoplankton was relatively important and was affected by the monsoon in winter. Compared with the corresponding δ13C values, the δ15N values exhibited a complex spatial distribution. By using a Bayesian mixing model, in the upper bay, the source of POM was mainly from marine organic matter (49%) in summer, and almost an equilibrated contribution of all sources in winter. In the middle bay and bay mouth, the POM contribution mainly originated from marine organic matter (53%) during the winter. In contrast, the POM source was mainly soil organic matter (63%) in summer, suggesting that the POM was sourced from the runoff from the upstream basin. Our results suggest that the seasonal shifts of the source of POM should be taken into account when estimating C or N mass balance in the monsoon-controlled bay.