There is no clear consensus about the pattern of cytokine production and regulation that causes patients with chronic schistosomiasis to develop severe hepatosplenic disease, which is characterized by peri-portal fibrosis and portal hypertension. Circulating immune complexes [CICs], play an important role in the pathogenesis of many clinical syndromes during the course of hepatic schistosomiasis.  Therefore, the aim of this study was to estimate interleukin-6 [IL-6] and tumor necrosis factor-α] levels in serum and ascetic fluid [AF] of schistosomal patients and to evaluate these cytokines response in relation to circulating immune complexes. Material and methods: The study enrolled 40 patients with hepatic schistosomiasis forming two groups; 20 patients with ascites [group I] and the other 20 patients without ascites [group II]. Apart from complete history taking, clinical examination, and routine laboratory work, blood and ascetic fluid [AF] samples were collected from the patients after hospital admission. Estimation of IL-6 and TNF-α in serum and AF according to the manufacturer instructions. Moreover, serum circulating immune complexes [CICs] were assayed as well. Results: The mean serum level of IL-6 was 156.9±150.82 pg/ml in schistosomal ascetic patients and 121.63±68.47 pg/ml in non-ascetic cases. The mean serum concentration of TNF-α was 88.5±70.59 pg/ml in group I and 66±46.76 pg/ml in group II patients. IL-6 concentration in the ascetic fluid of schistosomal patients had a mean of 284.4±280.08 pg/ml while ascetic fluid TNF-α had a mean of 113.25±58.97 pg/ml. Schistosomal patients with ascites were shown to have significantly higher levels of IL-6 and TNF-α in their ascetic fluid than in serum. A significant positive correlation was detected between the serum and AF concentrations of IL-6 [r-=0.559], and TNF-α [r-=0.556*], P<0.05 in each case. Ascitic patients had a significantly higher mean CIC [21.33±5.4 μg Eq/ml] than the non-ascitic cases [15.51±5.27 μg Eq/ml]. There was a significant positive correlation between serum level of IL-6 and CICs in schistosomal patients with ascites [r-=0.446*, P<0.05], and another significant positive correlation was demonstrated between ascetic fluid TNF-α and CICs in the same patients [r-=0.448*, P<0.05]. Conclusion: The study concluded that schistosomal patients with ascites had significantly higher levels of IL-6 and TNF-α in their ascetic fluid than in serum, while there was no significant difference between their serum levels in the ascetic and non-ascitic groups. Moreover, a significant positive correlation was detected between CICs and serum IL-6 in patients with ascites.