Objectives: Postdural puncture headache (PDPH) is a complication that may arise following spinal anesthesia. We investigated whether homocysteine and C-reactive protein levels may be associated in the development of PDPH in patients that received spinal anesthesia.Materials and Methods: In order to determine homocysteine and C-reactive protein (CRP) levels, blood samples were taken from patients before and one day following spinal anesthesia. A total of 100 male patients were enrolled in the study. The mean age of the patients was 29 years old. Out of all the patients, a total of 6 developed headaches. The Mann-Whitney U-test was used to compare homocysteine and CRP levels between patients that did and did not develop headaches. Results: Homocysteine levels before and after the operation were higher in subjects that developed a headache as compared to patients that did not develop headaches (p<0.001). CRP levels did not differ significantly between patients with headaches and patients that did not experience them (p>0.05). Conclusions: High blood levels of homocysteine in patients with PDPH might be used as a biomarker so to predict the development of PDPH. However, future larger, multi-center studies are needed to further elucidate this association.