To investigate the concentrations of nitric oxide (NO) products (NOx) and arginase activity in acute neuroinflammation, we analyzed cerebrospinal fluid (CSF) and plasma of clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS) patients, who were divided into groups on the basis of clinical and radiological disease activity. The NOx levels, in both, CSF and plasma, were increased in CIS (p = 0.0015, p = 0.0014, respectively) and RRMS group (p = 0.002, p = 0.0019, respectively), while arginase activity approached low levels, in CIS (p = 0.009, p = 0.02, respectively) and RRMS group (p = 0.018, p = 0.034, respectively) compared to controls. The NOx levels were higher in CSF and plasma of CIS than in RRMS group (p = 0.065, p = 0.037, respectively), inverse to arginase activity which was higher, in CSF and plasma, in RRMS than in CIS group (p = 0.031, p = 0.02, respectively). The CSF and plasma NOx values positively correlated with the clinical disease activity in CIS (r = 0.09, p = 0.81; r = 0.45, p = 0.023, respectively) and RRMS group (r = 0.311, p = 0.04; r = 0.512, p = 0.01, respectively). Also, CSF and plasma arginase activity showed negative correlation with clinical disease activity in CIS (r = 0.39, p = 0.03; r = 0.1, p = 0.65, respectively) and RRMS group (r = 0.43, p = 0.03; r = 0.62, p = 0.015, respectively). The CSF NOx levels showed positive correlation with volume of acute radiological lesions of CNS in CIS (r = 0.25, p = 0.045) and RRMS group (r = 0.31, p = 0.04), while arginase activity showed the negative correlations in CIS (r = 0.41; p = 0.035) and RRMS group (r = 0.52, p = 0.022). The results support NO and arginase involvement in the pathogenesis of acute neuroinflammation, which determination may be useful as surrogate markers for clinical and radiological disease activity.