An analytical relationship for the optimum design of continuous stirred tank reactors (CSTRâ€™s) in series performing phenol degradation was derived. The optimal design is based on the minimum overall reactor volume required for a certain degree of phenol removal. It is assumed that cell growth kinetics follow the Haldanes kinetics model with respect to phenol and with no oxygen limitation. The effect of operating parameters such as phenol inlet feed concentration, phenol removal efficiency and number of CSTRâ€™s in series on the optimum design are investigated. The design equations compared the volume required for a certain percentage of phenol removal for the optimum design and the equal volume design which is currently practiced design criteria. This study shows that the optimum design (variable volume reactors) is more efficient than equal volume design at relatively high inlet feed substrate concentration, high substrate conversion and increasing the number of reactors. The percentage of degree reduction in the total volume using the optimum design compared to equal size reactors can be up to 80 % depending on the operating parameters. Up to five CSTRs in series and PFR are described in this study. Experimental and kinetic data used in this optimization problem were collected from the literature.