The study area, Aetoliko Lagoon is a unique coastal Mediterranean landlocked ecosystem, controlled by tectonic activity and is characterized by permanent oxygen-depletion conditions (hypoxia/anoxia). The geological conditions, the geomorphology and the bathymetry of the lagoon, make the Aetoliko Lagoon an area of special interest for the research of the interplay between oxygen-depletion phenomena and human interference. Based on four research cruises within a time period of 1 year seasonal monitoring, in situ contemporary measurements in water column of physicochemical parameters pH, temperature (T, degrees C), salinity (S, parts per thousand), dissolved oxygen (DO) and redox potential (E-h) were taken, and laboratory analyses of total organic (TOC) and inorganic carbon (IC), total nitrogen (TN) and total phosphorus were carried out. The water column is divided in three major layers: The upper layer (0-10-m depth) with seasonal salinities between 18.5 and 21.5 parts per thousand; the middle layer (10-18.5-m depth) between 19.3 and 24.5 parts per thousand; and the lower one (18.5-30 m) between 22.5 and 25.6 parts per thousand. The lagoon's lower layer was extended below 18-m depth with almost constant temperature of around 14-15 degrees C. Anoxic conditions were recorded below 10-11-m depth in July and November, and below 14-m depth in February and April. The vertical distributions of IC and TN values were strongly anticorrelated with the vertical distributions of DO and pH-E-h values as the result of physical, chemical and biochemical procedures. The spatial lagoon sediment characteristics such as grain size and moment measures indicate that the lagoon sediments consists mainly of poorly to very poorly sorted fine-to-coarse silt and sandy mud rich in TOC, while the geochemical parameters indicated a partition in the northern and southern parts of the lagoon. The surface sediments of the lagoon bottom act as a 'reservoir' for the diachronic reload of the water column with nutrients and support the assumption that the human interference plays a secondary role in the ecological status of the lagoon.