AbstractAcidification and hypoxia are universal environmental issues in coastal seas, especially in large river estuaries such as the Pearl River estuary. In July and August of 2015, two legs of a field survey were conducted in the Pearl River plume. Leg 1 was sampled during the influence of upwelling favorable winds, while Leg 2 was during downwelling favorable winds. During both legs, instead of the typically observed dissolved inorganic carbon (DIC) consumption and dissolved oxygen (DO) over‐saturation, upwelling‐induced high DIC (>2,000 μmol kg−1), low pH (7.7–7.8) and low DO (140–150 μmol kg−1) values were observed in surface waters at the estuary mouth and the area off Hong Kong. In the bottom waters, hypoxia, acidification (pH 7.6–7.8) and DIC accumulation (DIC addition of ∼100–180 μmol kg−1) were observed. Hypoxia was less severe during Leg 2 compared to Leg 1. The stoichiometry of oxygen depletion to DIC addition was 0.89 for bottom water, suggesting remineralization was dominated by marine sourced organic matter. However, a comparison of data from the two legs showed that the stoichiometry of oxygen consumption to DIC accumulation was significantly higher during Leg 2 (0.73 ± 0.03 for Leg 1 vs. 0.80 ± 0.05 for Leg 2), although N/P ratios were the same (13.54 ± 1.93 for Leg 1 vs. 13.51 ± 2.04 for Leg 2). This phenomenon was attributed mainly to enhanced ventilation (re‐oxygenation) under the influence of the downwelling favorable winds during Leg 2. Although ventilation relieves some hypoxia, it might enhance acidification in bottom waters after a short‐term ventilation event. The enhanced acidification after short‐term ventilation is worthy of further study considering that most hypoxia and acidification are found in shallow coastal seas.