Abstract Study question Are SARS-CoV2 antibody isotypes detectable in seminal fluid of vaccinated men Summary answer Systemic circulating SARS-CoV2 antibodies are likely to be precluded from transport to seminal plasma following vaccination in males What is known already Expedited development of SARS-CoV-2 vaccines led to public concerns regarding impacts of the novel vaccine on gametes in patients seeking assisted reproduction. Recent studies on ovarian follicular fluid from women post SARS-CoV2 infection or BNT162b2 mRNA vaccination show similar levels of SARS-CoV2 IgG antibodies in follicular fluid as those found in serum. To our knowledge, no study to date has examined if SARS-CoV2 antibody isotypes are detectable in seminal fluid of vaccinated men. Study design, size, duration This was a longitudinal cohort study of 17 normospermic male patients attending a fertility clinic associated with a tertiary university maternity hospital. Semen and matched peripheral blood samples were collected prior to vaccination (t = 0), within 46 + 18.9 hours of vaccine completion (acute; t = 1) and at 88.4 + 12 days (3 months; t = 2) post vaccination. Participants/materials, setting, methods Serum and seminal plasma anti-SARS-CoV-2 spike isotypes (IgA, IgM and IgG1) and immune factors (IL-6, IL-8, IL-10, IFN-γ, TNF-α, IP-10; CXCL10, MCP-1, CCL2) were analysed using ELISA-based approaches at three time points. To rule out potential factors present in seminal plasma that could interfere with IgG detection, a commercial positive anti-Spike control was used to confirm detection in the ELISA assay. Self-reported symptoms and sperm parameters including count, motility, morphology, DNA damage were also quantified. Main results and the role of chance All semen samples were found to be negative for anti-SARS-CoV2 spike antibodies at all three time points indicating that systemic antibodies are likely precluded from transport to seminal plasma. Four out of 17 (23.5%) serum samples were negative for all three isotypes (IgM, IgA, IgG1) at < 72 hours post-vaccine completion, while one patient remained negative for all antibodies at 3 months post-vaccine. No global change from baseline was seen in reported symptoms, mean semen volume, semen pH, sperm concentration, motility, morphology or DNA damage in the acute or long phase. Two men showed a clinically relevant reduction in sperm motility alone in the acute phase that returned to normal by 3 months. Seminal plasma MCP-1 levels showed an acute but transient elevation post-vaccine, while IL-8 was marginally increased 3 months after completion of vaccination. Our findings also indicate a modest, positive correlation between serum levels of the anti-inflammatory cytokine IL-10 and self-reported symptoms in the acute post-vaccine period, with no correlation between serum IL-10 levels and change in sperm parameters from t = 0 to t = 1. Limitations, reasons for caution This study included a small population of only 17 men, all of whom were normospermic. Responses in men with subnormal baseline sperm parameters may differ and thus would be helpful to explore. Wider implications of the findings Our results show no significant adverse effect of vaccination. There may be temporary decline in sperm motility which could be more significant in men with poor baseline parameters. Further larger studies with inclusion of men with abnormal baseline parameters would be valuable to support timing of vaccination and treatment. Trial registration number not applicable