The study investigates the seasonal and spatial variations in water quality parameters at four different locations along Potou lagoon for seventeen consecutive months. In order to explore spatial variation among different stations and seasonal changes, no parametric test of ANOVA was used to compare the mean values of the tested parameters for all the different sampling sites and seasons. Seasonal observations on water quality parameters and chlorophyll-a in Potou coastal lagoon revealed that the coastal water was significantly influenced by freshwater during the long and short rainy seasons. The seasonal significant variation (p < 0.05) was generally recorded between the long dry season and the short rainy season. Temperature, salinity, pH, dissolved oxygen, transparency and chlorophyll-a increased during the long dry season, whereas, the concentration of nutrients (nitrite, nitrate, ammonium and soluble reactive phosphorus) increased in the rainy periods. Contrary to the seasonal variation, a spatial homogeneity (horizontal) was registered for all variables, a condition related to the low human occupation in the lagoon watershed. Comparing this study with others conducted in Potou lagoon in 2008, no critical differences that evidence alteration in the water quality were found.