The objective of this study was to assess the prevalence of sicca complex (SC) in patients with chronic hepatitis C virus (HCV) infection and its association with clinical and laboratory features of liver disease. Subjective and objective criteria of xerophthalmia and xerostomia were investigated in 120 HCV Egyptian patients. The lacrimal gland function was assessed by: tear film break-up time and lid parallel conjunctival folds test (LIPCOF), dacroscintigraphy (DSG) for lacrimal drainage and that of salivary glands by sialoscintigraphy. Sixty six of 120 patients (55%) had SC; all (100%) were proved to have xerostomia by sialoscintigraphy and xerophthalmia detected by ophthalmologic tests. Using dacroscintigraphy all SC patients (100%) were positive for lacrimal drainage abnormalities. Only 10.1% were symptomatic for SC. None of our patients had anti-Ro or anti-La antibodies. The presence of SC was associated with older age (r = 0.28, p = 0.00), female gender (p = 0.001), cirrhosis (r = 0.34, p = 0.00), thrombocytopenia (r = -0.72, p = 0.00), and rheumatologic manifestation (p = 0.000), but not with viral load (r = 0.19, p = 0.06). DSG showed significant statistical correlation with ophthalmologic tests (r = 0.87, p = 0.00). High prevalence of SC in HCV Egyptian patients was detected. LIPCOF and DSG are objective and noninvasive methods for early diagnosis of xerophthalmia and assessment of the nasolacrimal drainage, respectively. Hindrance of lacrimal drainage proved by DSG was frequently encountered in HCV patients with SC (100%) and strongly correlated with xerophthalmia.