Molecular timing mechanisms known as circadian clocks drive endogenous 24h rhythmicity in most physiological functions, including innate and adaptive immunity. Consequently, the response to immune challenge such as vaccination might depend on the time of day of exposure. This study assessed whether the time-of-day of vaccination (TODV) is associated with the subsequent immune and clinical response by conducting a systematic review of previous studies. The Cochrane Library, Pubmed, Google, Medline and Embase were searched for studies that reported time-of-day of vaccination and immune and clinical outcomes, yielding 3,114 studies; 23 of which met the inclusion criteria. The global SARS-CoV-2 vaccination programme facilitated investigation of TODV and almost half of the studies included reported data collected during the COVID-19 pandemic. There was considerable heterogeneity in the demography of participants and type of vaccine and most studies were biased by failure to account for immune status prior to vaccination, self-selection of vaccination time, or confounding factors such as sleep, chronotype and shiftwork. The optimum TODV was concluded to be afternoon (five studies), morning (five studies), morning and afternoon (1 study), midday (1 study) and morning or late afternoon (1 study) with the remining 10 studies reporting no effect. Further research is required to understand the relationship between TODV and subsequent immune outcome, and whether any clinical benefit outweighs the potential effect of this intervention on vaccine uptake.