This paper covers spatial and temporal variation in phytoplankton communities and physico-chemical variables in the Can Gio Mangrove Biosphere Reserve (CGMBR), Vietnam, based on field measurement conducted monthly at nine stations during February 2009 to January 2010. Species diversity, richness and phytoplankton abundance were calculated. Canonical Correspondence Analysis (CCA) was used to investigate the relationship between environmental factors and phytoplankton community. A total of 126 species were recorded with a clear dominance of Bacillariophyceae, which formed about 76.4% of the total phytoplankton counts with an annual average of 44.900 cells/L. Other algal classes like Dinophyceae, Cyanophyceae and Chrysophyceae sustained low counts, forming collectively about 14% of the total abundance of phytoplankton. Although Chaetoceros and Coscinodiscus were the most dominant genera, Schroederella and Skeletonema showed high abundance during the studied period. Among the nine environmental parameters tested in this study, salinity, nitrate and ammonium were found to be significantly different between two seasons. On the other hand, no significant difference was found between stations for the studied variables. Results of CCA indicated that phytoplankton assemblage in the CGMBR was influenced by salinity, nitrate and phosphate concentration. This is the first study simultaneously investigating the phytoplankton communities and their environment in this area and it is essential in order to set up the baseline of future studies.