Objective: The treatment of choice for odontogenic cysts is surgery, and when the cysts are infected, preoperative antibiotic coverage is needed. However, the diffusion of antibiotics is a matter of controversy because of the low vascularization of the cystic epithelium. The aim of the present study was to determine the antimicrobial action of amoxicillin and metronidazole on infected odontogenic cysts. Methods and Materials: Ten odontogenic root cysts were punctured before and after antibiotic treatment in 2 patient groups. Group 1 consisted of 5 patients treated with 500 mg amoxicillin at 6-hour intervals, and group 2 consisted of 5 patients treated with 400 mg metronidazole at 8-hour intervals, for 7 days. After this period, the patients were submitted to surgery for enucleation. The fluid collected was seeded onto culture media for counts of total bacteria and facultative anaerobic bacteria. Results: The results showed that the amount of bacteria present in the fluid was significantly higher than the amount isolated after antibiotic treatment. Also, most of the microorganisms present in the fluid collected before antibiotic administration were strict anaerobes. Conclusions: Both antibiotics reduced the number of bacteria in the cystic fluid, showing that they did diffuse into the lesions at sufficient concentrations to exert their antimicrobial action. Keywords: amoxicillin, metronidazole, odontogenic cyst, odontogenic infection