Aim: Experimental studies suggest that central sensitization plays important role in the pathophysiology of chronic pain and chronic tension-type headache (CTTH). Studies on pro-inflammatory cytokines, interleukin (IL)-1__ampersandsignbeta; and tumor necrosis factor (TNF)-__ampersandsignalpha; serum levels during headache attack showed inconsistent results. This study was aimed to see the serum levels of TNF-__ampersandsignalpha;, IL-1, IL-6 in patients with CTTH and its correlation with pain intensity. Methodology: This cross-sectional study was conducted at the Adam Malik Hospital and Bukit Barisan II Army Hospital from January 2013 to June 2014 after approved by the Ethics Committee for Health Research University of North Sumatera School of Medicine. The subjects were recruited consecutively from study population and agree to participate in this study. Diagnosis of CTTH was conducted through anamnesis, physical and neurological examination and based on the diagnostic criteria as stated in the ICH X. Subjects underwent physical and neurological examination, including assessment of pain intensity by using the Numeric Rating Scale ( NRS ) for pain. Furthermore, venous blood was taken to measure serum levels of TNF-__ampersandsignalpha; , IL-1, and IL-6. Results: The mean of TNF-__ampersandsignalpha; serum level is 1.81528 pg/dl (SD __ampersandsignplusmn; 0.890686), whereas the mean of IL__ampersandsignndash;1 serum level is 0.20226 pg/dl (SD __ampersandsignplusmn; 0.193930), and the mean value of IL-6 serum level is 1.45089 pg/dl (SD __ampersandsignplusmn; 1.189502). There was very weak positive correlation (r=0.035) and non-significant (p=0.806) between NRS scores and TNF-__ampersandsignalpha; serum levels. There was a nonsignificant (p=0.793) and very weak negative correlation (r =-0037) between NRS scores and IL-1 serum level. NRS scores have a very weak negative correlation (r=-0.107) and also not statistically significant (p=0.447) with IL-6 serum level. Conclusions: Previous studies showed a positive correlation between NRS score and levels of TNF-__ampersandsignalpha;, IL-1 and IL-6. The higher NRS score, the higher serum level of TNF-__ampersandsignalpha;, IL-1 and IL-6. This study shows weak negative correlation between NRS scores and IL-1 and IL-6 serum level. A positive weak correlation only found between NRS scores and TNF-__ampersandsignalpha; serum level. All of these correlations were statistically nonsignificant. These findings perhaps because the sample from serum did not describe the biological mechanisms that occur in the brain.