Athletes are advised to receive the COVID-19 vaccination to protect themselves from SARS-CoV-2 infection during major competitions. Despite this, many athletes are reluctant to get the COVID-19 vaccine due to concerns that symptoms of vaccinosis may impair athletic performance. This study aimed to determine the effects of COVID-19 vaccination on the physiological responses to graded exercise. Healthy physically active participants completed a 20-min bout of graded cycling exercise at intensities corresponding to 50%, 60%, 70%, and 80% of the predetermined V̇O2max before and ∼21 days after receiving the COVID-19 vaccine (2-dose Pfizer mRNA or 1-dose Johnson & Johnson). Vaccination had no effect on a large number of physiological responses to exercise measured in blood (e.g., lactate, epinephrine, and cortisol) and by respiratory gas exchange (e.g., oxygen uptake, CO2 production, ventilation, respiratory exchange ratio, predicted V̇O2max, and ventilatory threshold) (P > 0.05). We did, however, find significant elevations in heart rate (∼5 beats/min) and norepinephrine (P = 0.006 and 0.04, respectively) in response to vigorous (i.e., 70%-80% V̇O2max) intensity exercise after vaccination, particularly in those who received the two-shot Pfizer mRNA vaccine regimen. These findings held true when compared with demographically matched controls who completed identical bouts of exercise several weeks apart without receiving a vaccine; delta values for heart rate (P = 0.03) and norepinephrine (P = 0.01) were elevated in the second trial for those who received the Pfizer mRNA vaccine compared with the controls at the 70% and 80% V̇O2max stages, respectively. Recent COVID-19 vaccination has minimal effects on the physiological responses to graded exercise in physically active healthy people. The small elevations in cardiovascular and neuroendocrine responses to exercise after the Pfizer mRNA vaccine regimen could have implications for athletes at the elite level and warrants investigation.NEW & NOTEWORTHY Recent COVID-19 vaccination does not affect a large number of physiological responses to graded exercise, indicating that vaccination is unlikely to impair exercise capacity in normal healthy people. Heart rate and norepinephrine levels were elevated in response to exercise after the two-dose Pfizer mRNA vaccination compared to controls. Small elevations in cardiovascular and neuroendocrine responses to exercise after recent COVID-19 vaccination could have implications for exercise performance in elite athletes and warrants investigation.