Observations suggest that the tropical Pacific Ocean has lost oxygen since the 1960s leading to the expansion of its oxygen minimum zone (OMZ). Attribution to anthropogenic forcing is, however, difficult because of limited data availability and the large natural variability introduced by the Pacific Decadal Oscillation (PDO). Here, we evaluate the PDO influence on oxygen dynamics and OMZ extent using observations and hindcast simulations from two global ocean circulation models (NEMO-PISCES, MOM6-COBALT). In both models, the tropical Pacific oxygen content decreases by about 30 Tmol.decade$^{-1}$ and the OMZ volume expands by $1.3\times10^5$ km$^3$.decade$^{-1}$ during PDO positive phases, while variations of similar magnitude but opposite sign are simulated during negative phases. Changes in equatorial advective oxygen supply, partially offset by biological demand, control the oxygen response to PDO. Observations which cover 39\% of the tropical Pacific volume only partially capture spatio-temporal variability, hindering the separation of anthropogenic trend from natural variations.