The resurgence of syphilis across Europe has led to a growing number of atypical cases, often characterised by varied symptoms that can delay diagnosis. We report the case of a young man who has sex with men (MSM), presenting with persistent headaches and swelling of the forehead suggestive of giant cell arteritis (GCA). Despite a recent negative syphilis test, further investigations confirmed the diagnosis of neurosyphilis. The patient had been using doxycycline post-exposure prophylaxis (DoxyPEP), which is suspected to have delayed the diagnosis by masking the typical antibody response. This case highlights concerns about DoxyPEP’s impact on syphilis detection and disease progression. Further research is warranted to explore its effects on antimicrobial resistance, the human microbiome, and clinical outcomes.