OBJECTIVES: Epidemiological treatment for suspected Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections is recommended for exposed partners before laboratory confirmation, within 14 days of exposure to reduce symptoms, break transmission chains, and prevent loss of follow-up. This approach may lead to potential antibiotic overuse by uninfected individuals, thereby enhancing antimicrobial resistance. This study investigated the accuracy of epidemiological treatment for CT and NG. PATIENTS AND METHODS: Retrospective cross-sectional analysis conducted on asymptomatic exposed partners presumptively treated for CT and/or NG in Lyon's Sexual Health Clinics between January and December 2023. The positive test rate results of exposed and treated patients were assessed, along with the frequency of potential antibiotic overuse (i.e., receiving at least one unnecessary antibiotic treatment). The association of potential antibiotic overuse with pre-exposure prophylaxis for HIV, age, gender, sexual orientation, and type of contact was also evaluated. RESULTS: Among 141 patients who received epidemiological treatment, the concordance rate between the test and the reported exposure was 44.8 % for CT and 28.1 % for NG. The proportion of potential antibiotic overuse was 59.6 % (84/141). Potential antibiotic overuse was less common among patients exposed to CT than NG (p = 0.006). Self-identified women (compared with men) and heterosexual (compared with those with other sexual orientations) experienced lower rates of potential antibiotic overuse (p = 0.045 and 0.003, respectively). CONCLUSION: Given the good follow-up at our clinics, waiting for the laboratory diagnosis before initiation of treatment appears reasonable and would avoid nearly 60% of unnecessary antibiotic treatments in CT and/or NG asymptomatic exposed partners.