This book constitutes the refereed proceedings of the 13th International Conference on Computational Methods in Systems Biology, CMSB 2015, held in Nantes, France, in September 2015. The 20 full papers and 2 short papers presented were carefully reviewed and selected from 43 full and 4 short paper submissions. The papers cover a wide range of topics in the analysis of biological systems, networks and data such as model checking, shastic analysis, hybrid systems, circadian clock, time series data, logic programming, and constraints solving ranging from intercellular to multiscale.