In the period 1987–2017, a series of physical and chemical measurements related to oxygen variability at a trough area with a maximum depth of ~420 m in the West Saronikos Gulf, reveal the following: In the early 90s, deep winter mixing occurred resulting in an oxygenation down to ~420 m followed by an oxygen decline. This decline reached near-bottom hypoxic conditions (O2 < ~62 μM (μmol/L)) after 1998, while a denitrification phase occurred after 2000 and a complete bottom anoxia in 2005. In June 2012, an oxygenation down to ~350 m was detected that most likely occurred in winter 2012. The 2012 oxygenation raised the until-then anoxic bottom concentrations to hypoxic ones in the years towards 2017 via vertical diffusive oxygen transfer. Observations of the benthic communities during the hypoxia, severe hypoxia (O2 < ~15 μM) and oxygen recovery phases showed a peak of opportunists in the hypoxia and a long faunal depletion in the severe hypoxia phases. A reversal in the benthic community structure appeared after the oxygenation of 2012 with the (re)appearance of opportunists while, in 2017, the community showed signs of retreat to earlier stages. The main anthropogenic pressure that could tentatively affect the oxygen concentration in the study area is posed by the Athens treated-sewage outfall at ~40 km away from the trough, which inputs organic matter into the Saronikos Gulf through effluent water of reduced salinity that, in addition, may alter the stratification opposing the vertical mixing. We show that the treated sewage output had no influence on a) the stratification, b) the particulate and dissolved organic carbon and c) the sewage-derived organic matter. Instead, the long-term dissolved oxygen variability with the deep renewal events was mostly driven by the large-scale atmosphere-ocean conditions (heat exchange and evaporation-minus-precipitation budget) that determine the hydrographic characteristics and the winter mixing.