The characteristics of ascites in patients with POEMS syndrome, which comprise polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes, are unknown. We described the frequency of ascites at presentation of POEMS syndrome and further evaluated for the pathogenesis and nature of the ascites. One hundred and six consecutive patients with POEMS syndrome in Chinese PLA General Hospital were evaluated for the presence of ascites, and the cellular and biochemical characteristics of the ascitic fluids were assessed. Serum levels of complement, cytokines, and clinical chemistry parameters were analyzed in peripheral blood samples of the patients with POEMS syndrome. Ascites was observed in 42 of 106 (39.6 %) patients with POEMS syndrome. Patients with ascites had significantly high serum levels of C3 and C4 complement components and TNF-α (all p < 0.01). In 31 (73.8 %) patients who underwent paracentesis, the ascitic fluids had low serum ascites albumin gradients (SAAG), indicating non-portal hypertension. Spontaneous bacterial peritonitis was not observed. Ascites is a common complication of POEMS syndrome and has characteristics of non-portal hypertension, based on low SAAG. Increased immune activation and inflammatory status could contribute to the pathogenesis of ascites in POEMS syndrome.