COVID-19 causes cardiovascular and lung problems that can be aggravated by confinement, but the practice of physical activity (PA) could lessen these effects. The objective of this study was to evaluate the association of maximum oxygen consumption (VO2max) with vaccination and PCR tests in apparently healthy Chilean adults. An observational and cross-sectional study was performed, in which 557 people from south-central Chile participated, who answered an online questionnaire on the control of COVID-19, demographic data, lifestyles, and diagnosis of non-communicable diseases. VO2max was estimated with an abbreviated method. With respect to the unvaccinated, those who received the first (OR:0.52 [CI:0.29;0.95], p = 0.019) and second vaccine (OR:0.33 [CI:0.18;0.59], p = 0.0001) were less likely to have an increased . VO2max. The first vaccine was inversely associ- ated with . VO2max (mL/kg/min) (β:−1.68 [CI:−3.06; −0.3], p = 0.017), adjusted for BMI (β:−1.37 [CI:−2.71; −0.03], p = 0.044) and by demographic variables (β:−1.82 [CI:−3.18; −0.46], p = 0.009); similarly occur for the second vaccine (β: between −2.54 and −3.44, p < 0.001) on models with and without adjustment. Having taken a PCR test was not significantly associated with VO2max (mL/kg/min). It is concluded that vaccination significantly decreased . VO2max, although it did not indicate cause and effect. There is little evidence of this interaction, although the results suggest an association, since V O2max could prevent and attenuate the contagion symptoms and effects.