Aim The aim of this study was to determine IL-1β and TNF-α levels in periapical exudates and to evaluate their relationship with clinical and radiological findings. Methodology Periapical exudates were collected from root canals of 35 single-rooted teeth using absorbent paper points. IL-1β and TNF-α levels were determined by enzyme-linked immunosorbent assays. The samples were divided into two groups according to the presence or absence of clinical signs including swelling and/or fistula, pain on palpation and/or percussion, and pus discharge from canals. Periapical exudate samples were divided into two groups according to size of periapical radiolucent area. Results The mean concentration of IL-1β (72.79 ng mL-1) in periapical exudates was approximately 12-fold higher than TNF-α (6.17 ng mL-1). There was no significant correlation between these cytokines (P > 0.05). IL-1β levels in canals with larger radiolucent areas (long axis ≥1 cm) were significantly higher than those with small areas (P < 0.05). There was a tendency toward higher levels of IL-1β in groups with clinical signs, but the differences were not significant (P > 0.05). Conclusions Periapical exudate levels of both cytokines failed to reflect periapical disease state.