The importance of oxidative stress in the pathogenesis of neuroimmunological and neurodegenerative diseases, such as multiple sclerosis (MS), has been discussed for a long time. However, markers for oxidative stress in cerebrospinal fluid are hardly detected. The aim of the present study is to assess whether carbonyl proteins as end products of metabolic processes may serve as a marker for oxidative stress in the cerebrospinal fluid (CSF) of patients with neuroimmunological and neurodegenerative diseases. Levels of carbonyl proteins in the CSF were assessed in 15 patients suffering from MS, four patients with neurodegenerative diseases, including one patient with dementia complicated by carcinomatous meningitis due to breast cancer, and four control subjects with no established neurological disease. Levels of carbonyl proteins were measured with a commercially available KIT. A significant difference (P = 0.025) was shown for mean values of various subgroups with highest levels for patients with neurodegenerative diseases (756.1 pmol/mg), followed by the MS (630.8 pmol/mg) and the control group (356.5 pmol/mg). Post-hoc pair wise comparisons showed significant differences between the MS group and healthy controls (P = 0.016) as well as for patients with neurodegenerative diseases and healthy controls (P = 0.02). This pilot trial showed that carbonyl proteins might serve as measure for oxidative stress in the CSF of relapsing as well as progressive MS patients and in patients with neurodegenerative diseases. Larger trials have to show whether they may serve as biomarkers and be helpful in monitoring patients with MS or neurodegenerative diseases.