In this study, the authors assessed cerebrospinal fluid cytokine levels and single-photon emission computed tomography (SPECT) findings in complex febrile seizures. This study included 23 Japanese patients with complex febrile seizures. Twenty patients underwent SPECT and 12 underwent analysis of cerebrospinal fluid cytokine levels (interleukin [IL]-6, interleukin-10, interleukin-17, interleukin-1β, tumor necrosis factor–α, and interferon-γ); 9 patients underwent both studies. Cerebrospinal fluid cytokine levels were compared between the current complex febrile seizure patients and 30 patients with acute encephalopathy. In 17 of 20 patients, SPECT findings revealed areas of hypoperfusion, including the frontal (5), occipital (4), and lobular (4) regions, overlapping with other areas. Relative to patients with acute encephalopathy, those with complex febrile seizures exhibited significantly lower cerebrospinal fluid interleukin-6, interleukin-1β, tumor necrosis factor–α, and interleukin-10 levels and significantly higher interleukin-17 levels. As patients with complex febrile seizures frequently exhibit abnormal SPECT findings, cerebrospinal fluid interleukin-17 levels might provide a valid biomarker to discriminate complex febrile seizures and acute encephalopathy, regardless of SPECT findings.