Hepatic steatosis affects disease progression in patients with chronic hepatitis C virus (HCV) infection. We investigated the plasma sphingolipid profile in patients with chronic hepatitis C (CHC) and whether there was an association between HCV-related steatosis and plasma sphingolipids. We used high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze plasma sphingolipids in 120 interferon-naïve, non-diabetic, and non-obese CHC patients. Hepatic steatosis was defined as ≥5 % hepatocytes with fat based on histopathological analysis. Blood biochemical indicators and HCV load and genotype were also determined. Thirty-six (30.0 %) of 120 patients presented with hepatic steatosis Grades 1-3. Forty-four plasma sphingolipids were detected. Plasma sphingomyelin (SM) (d18:1/22:0) and ceramide (Cer) (d18:1/24:0)-1-P correlated with steatosis grade (r = 0.22, p = 0.015; r = -0.23, p = 0.012, respectively). SM (d18:1/22:0) [odds ratio (OR) = 1.12] and Cer (d18:1/24:0)-1-P (OR = 0.88) were independent factors for the presence of hepatic steatosis in CHC patients. The area under the curve (AUC) of SM (d18:1/22:0) and Cer (d18:1/24:0)-1-P was 0.637 and 0.638, respectively, to identify the presence of steatosis. Further analysis for genotype 2 CHC showed that only SM (d18:1/22:0) was independently linked to steatosis (OR = 1.21). The AUC of SM (d18:1/22:0) to identify hepatic steatosis in genotype 2 CHC was 0.726. Its sensitivity and negative predictive value reached 0.813 and 0.886, respectively. This study suggested that altered plasma SM (d18:1/22:0) was closely related to hepatic steatosis in chronic HCV infection, especially with genotype 2. Experimental studies are needed to determine further the underlying mechanisms responsible for these associations.