The relationship between residence time and oxygen saturation was investigated in a mesotidal lagoon in southern Portugal. The system receives no significant freshwater input during the summer months and has a high evaporation rate. These features enable an estimate of residence time from the salinity differences between ocean water entering the system and lagoon water. More than 10,000 GPS referenced measurements of oxygen saturation, temperature and salinity were made during large spring tides in September, 2006. The lowest oxygen saturation ( approximately 44%) was measured in the waters with the highest calculated residence times (7 days). There was a significant linear decrease in the oxygen saturation with increasing residence time of approximately 16% per day. This was similar to the rate measured on a neap tide in August, 2005. The high salinity, low oxygen saturated water was spatially confined to one inner channel, except at high water when this water was pushed into other channels. Although the tides investigated were the largest for several years, the oxygen saturation did not exceed 70% in this inner region. It is proposed that the direct discharge of oxygen consuming effluent, including domestic sewage, into this inner channel is responsible for this persistent oxygen deficit.