Objectives: To assess the frequency and intensity of [¹⁸F]-prostate-specific membrane antigen (PSMA)-1007 axillary uptake in lymph nodes ipsilateral to COVID-19 vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) in patients with prostate cancer referred for oncological [¹⁸F]-PSMA positron emission tomography (PET)/CT or PET/MR imaging. Methods: 126 patients undergoing [¹⁸F]-PSMA PET/CT or PET/MR imaging were retrospectively included. [¹⁸F]-PSMA activity (maximum standardized uptake value) of ipsilateral axillary lymph nodes was measured and compared with the non-vaccinated contralateral side and with a non-vaccinated negative control group. [¹⁸F]-PSMA active lymph node metastases were measured to serve as quantitative reference. Results: There was a significant difference in maximum standardized uptake value in ipsilateral and compared to contralateral axillary lymph nodes in the vaccination group (n = 63, p < 0.001) and no such difference in the non-vaccinated control group (n = 63, p = 0.379). Vaccinated patients showed mildly increased axillary lymph node [¹⁸F]-PSMA uptake as compared to non-vaccinated patients (p = 0.03). [¹⁸F]-PSMA activity of of lymph node metastases was significantly higher (p < 0.001) compared to axillary lymph nodes of vaccinated patients. Conclusion: Our data suggest mildly increased [¹⁸F]-PSMA uptake after COVID-19 vaccination in ipsilateral axillary lymph nodes. However, given the significantly higher [¹⁸F]-PSMA uptake of prostatic lymph node metastases compared to “reactive” nodes after COVID-19 vaccination, no therapeutic and diagnostic dilemma is to be expected. Advances in knowledge: No specific preparations or precautions (e.g. adaption of vaccination scheduling) need to be undertaken in patients undergoing [¹⁸F]-PSMA PET imaging after COVID-19 vaccination.