Dissolved organic matter (DOM) derived from mariculture has been recognized as a key driver triggering coastal harmful algal blooms (HABs), particularly favoring the growth of mixotrophic algae species. Yet, it remains unclear how DOM derived from diverse sources drives the proliferation and modulates the cellular metabolism of Karenia mikimotoi, a notorious bloom-forming species in mariculture areas. Here, using in situ seawater and sediment leachate from kelp, large yellow croaker, and oyster farming areas in Sansha Bay (Fujian, China) as the sole medium, we investigated the physiological response and metabolic dynamics of K. mikimotoi cells exposed to distinct mariculture-derived DOM. Comparative experimental results show that sediment leachate significantly promotes cell growth, whereas in situ seawater from the mariculture area has a very limited effect on growth. Moreover, in the parallel experiments within each DOM groups, the algal cell density was higher in the antibiotic-treated groups, suggesting a potential competitive effect between phycosphere bacteria and algal cells for DOM utilization. Further comparative transcriptomics revealed that cellular metabolic pathways associated with genetic information processing were widely downregulated in the cells subjected to antibiotics treatment. Concurrently, sediment DOM markedly activated metabolic pathways related to growth and metabolic processes. These results indicate that in mariculture waters, sediment-derived DOM serves as a potential nutrient source for algal proliferation and shape the dynamic cellular metabolism in response to DOM assimilation. Meanwhile, the potential competes imposed by phycosphere bacteria result in additional metabolic costs in algal cells. This study provides deeper insights into the mechanisms driving Karenia mikimotoi blooms.