Posthemorrhagic hydrocephalus (PHHC) represents a major complication of preterm birth. The aim of this study was to determine whether cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines IL-1beta, IL-18, and interferon (IFN)-gamma are altered in the CSF of preterm infants with PHHC and may serve as a marker of white matter damage (WMD). Twenty-seven preterm infants with PHHC were included in the study; 13 of them had signs of cystic WMD (cWMD) on ultrasound examinations. CSF sample 1 was obtained at first ventriculostomy, sample 2 at shunt implantation. Results were compared with a control group of 20 age-matched patients without neurologic diseases. IL-1beta concentrations were elevated in CSF sample 1 of PHHC patients without WMD and in sample 1 of patients with cWMD. Concentrations of IL-18 were increased in both samples of patients without WMD and in sample 2 of patients with cWMD. CSF levels of IFN-gamma were elevated in sample 1 of PHHC patients with cWMD. The pro-inflammatory cytokine IL-1beta and IL-18 levels in the CSF are elevated in patients with PHHC. Higher IFN-gamma levels are detected in a subgroup of patients developing cWMD, indicating its involvement in the pathogenesis of cWMD in the context of PHHC.