Abstract. Observations and model runs indicate trends in dissolved oxygen (DO) associated with current and ongoing global warming. However, a large-scale observation-to-model comparison has been missing and is presented here. This study presents a first global compilation of DO measurements covering the last 50 yr. It shows declining upper-ocean DO levels in many regions, especially the tropical oceans, whereas areas with increasing trends are found in the subtropics and in some subpolar regions. For the Atlantic Ocean south of 20° N, the DO history could even be extended back to about 70 yr, showing decreasing DO in the subtropical South Atlantic. The global mean DO trend between 50° S and 50° N at 300 dbar for the period 1960 to 2010 is –0.066 μmol kg⁻¹ yr⁻¹. Results of a numerical biogeochemical Earth system model reveal that the magnitude of the observed change is consistent with CO₂-induced climate change. However, the pattern correlation between simulated and observed patterns of past DO change is negative, indicating that the model does not correctly reproduce the processes responsible for observed regional oxygen changes in the past 50 yr. A negative pattern correlation is also obtained for model configurations with particularly low and particularly high diapycnal mixing, for a configuration that assumes a CO₂-induced enhancement of the C : N ratios of exported organic matter and irrespective of whether climatological or realistic winds from reanalysis products are used to force the model. Depending on the model configuration the 300 dbar DO trend between 50° S and 50° N is −0.027 to –0.047 μmol kg⁻¹ yr⁻¹ for climatological wind forcing, with a much larger range of –0.083 to +0.027 μmol kg⁻¹ yr⁻¹ for different initializations of sensitivity runs with reanalysis wind forcing. Although numerical models reproduce the overall sign and, to some extent, magnitude of observed ocean deoxygenation, this degree of realism does not necessarily apply to simulated regional patterns and the representation of processes involved in their generation. Further analysis of the processes that can explain the discrepancies between observed and modeled DO trends is required to better understand the climate sensitivity of oceanic oxygen fields and predict potential DO changes in the future.