To study serum levels of leptin and adiponectin in patients with chronic hepatitis C virus infection genotype-4 (HCV-4) related steatosis and fibrosis. We prospectively studied 45 untreated men with chronic HCV-4, with proven steatosis (group I, 30 patients), and fibrosis (group II, 15 patients), on liver biopsy. In addition, 15 healthy men (group III), matched for age, and body mass index were included. However, we excluded another five patients with steatohepatitis, and six patients with cirrhosis. We measured total serum leptin and adiponectin levels, as potential predictors for liver steatosis and fibrosis. Also, a correlation between these adipokines and various clinical and laboratory data were evaluated. All subjects were selected from Tropical and Internal medicine departments, Menoufiya University Hospital, Menoufiya, Egypt, during the period from February 2010 to August 2011. In group I, severity of hepatic steatosis was mild, moderate, and severe, in 19 patients (63.5%), 8 patients (26.5%), and 3 patients (10%), respectively. In contrast, in group II, hepatic fibrosis was found to be in stage 1, 2, and 3, in 6 patients (40%), in 6 patients (40%), and in 3 patients (20%), respectively. On comparing group I with group II, there was a significant decrease in serum adiponectin levels (131.4 ± 7.91 pg/mL vs 436 ± 9.75 pg/mL, P < 0.001), while there was no significant difference between both groups regarding serum leptin levels (34.69 ± 7.69 ng/mL vs 35.17 ± 1.06 ng/mL, P > 0.05). However, in the same group, when compared with group III, there was a significant increase in serum leptin levels (34.69 ± 7.69 ng/mL vs 10.69 ± 0.84 ng/mL, P < 0.001), while there was a significant decrease in serum adiponectin levels (131.4 ± 7.91 pg/mL vs 342.4 ± 44.48 pg/mL, P < 0.001). In contrast, in group II, when compared with group III, there was a significant increase in serum leptin and adiponectin levels (35.17 ± 1.06 ng/mL vs 10.69 ± 0.84 ng/mL, P < 0.001, and 436 ± 9.75 pg /mL vs 342.4 ± 44.48 pg/mL, P < 0.05, respectively), while there was no significant difference between both groups regarding serum creatinine (0.83 ± 0.34 vs 0.89 ± 0.24, P > 0.05). On the other hand, serum leptin was not correlated with serum adiponectin in group I and in group II (r = 0.09, P > 0.05, and r = -0.1, P > 0.05, respectively). However, serum adiponectin was significantly negatively correlated with serum aspartate transaminase in group I, but no correlation detected in group II (r =-0.39, P > 0.05, and r = -0.03, P > 0.05). In male patients with chronic HCV-4, serum adiponectin levels are elevated in hepatic fibrosis, but decreased in steatosis. Therefore, in contrast to leptin, adiponectin may be used as a non-invasive marker.