Abstract In this study, the variables of zooplankton and water quality were investigated in the Can Giuoc River, Southern Vietnam. Zooplankton was monitored in April and September 2015 at 5 sampling sites in the river. Some basic water quality parameters were also tested, including pH, total suspended solid (TSS), dissolved oxygen (DO), biological oxygen demand (BOD5), inorganic nitrogen (NH4+), dissolved phosphorus (PO43−), and coliform. The zooplankton biodiversity indices were applied for the water quality assessment. The results showed that pH ranged from 6.7 to 7.6 during the monitoring. The TSSs were between 34–117 mg/L. The DO and BOD5 were from 0.6 to 3.8 mg/L and from 6.3 to 13.2 mg/L, respectively. The NH4+ and PO43− concentrations ranged from 0.44 to 3.23 and from 0.08 to 1.85 mg/L, respectively. The coliform number was between 9.3×103–9.3×104 MPN/100 mL. The zooplankton analyses showed that there were 31 species of coelenterates, rotatoria, oligochaetes, cladocerans, copepods, ostracods, mysidacea, and 8 larval types. Thereof, the species of copepods were dominant in the species number. The zooplankton density ranged from 9 500 to 23 600 individuals/m3 with the main dominant species of Moina dubia (Cladocera), Thermocyclops hyalinus, Acartia clausi, Oithona similis (Copepoda), and nauplius copepods. The biodiversity index values during the monitoring were from 1.47 to 1.79 characteristic of mesotrophic conditions of the aquatic environment. Besides, the species richness positively correlated with pH, TSS, DO, BOD5, NH4+, PO43−, and coliform, while the zooplankton densities got a positive correlation with DO, BOD5, NH4+, PO43−, and coliform. The results confirmed the advantage of using zooplankton and its indices for water quality assessment.