This study investigates the impact of 5Es Problem-Solving Model on science process-skills acquisition, performance and retention in Cell Physiology among Secondary School Biology Students in Zaria Education Zone, Kaduna State, Nigeria. The study adopts a Quasi-Experimental Design of Pretest- Posttest, Non-Equivalent Groups. The population comprised all 7,807 SS2 Biology students from 30 public Senior Secondary Schools in Zaria Education Zone. A sample of 110 students from two randomly selected coeducational schools was used for the study. The study involves two groups. The experimental group was taught Cell Physiology using 5Es Model while the Control Group was exposed to the same concept using Conventional Method. Two validated instruments were used for data collection, namely, Science Process Skills Acquisition Test (SPSAT) and Cell Physiology Performance Test (CPPT).These have reliability coefficients of 0.84 and 0.89 respectively,estimated using Pearson Product Moment Correlation (PPMC) statistic. Six research questions and six null hypotheses guided this study. Research questions were answered using Mean and Standard Deviation statistics while null hypotheses were tested using Independent Samples t-test at 0.05 level of significance.Findings reveal a significant difference between the mean scores of experimental and control groups in their science processskills acquisition, performance and retention, all in favour of the experimental group. The results also show that male and female students in the experimental group do not significantly differ in the variables studied. Based on these findings, the researcher concludes that the 5EsModel is effective and gender-friendly infosteringthe examined variables among secondary school Biology students. It is therefore recommended that Biology teachers frequently employ this model in teaching challenging concepts in Biology like Cell Physiology.