The fate of soil carbon and nitrogen compounds in soils in response to climate change is currently the object of significant research. In particular, there is much interest in the development of a new generation of micro-scale models of soil ecosystems processes. Crucial to the elaboration of such models is the ability to describe the growth and metabolism of small numbers of individual microorganisms, distributed in a highly heterogeneous environment. In this context, the key objective of the research described in this article was to further develop an individual-based soil organic matter model, INDISIM-SOM, first proposed a few years ago, and to assess its performance with a broader experimental data set than previously considered. INDISIM-SOM models the dynamics and evolution of carbon and nitrogen associated with organic matter in soils. The model involves a number of state variables and parameters related to soil organic matter and microbial activity, including growth and decay of microbial biomass, temporal evolutions of easily hydrolysable N, mineral N in ammonium and nitrate, CO2 and O2. The present article concentrates on the biotic components of the model. Simulation results demonstrate that the model can be calibrated to provide good fit to experimental data from laboratory incubation experiments performed on three different types of Mediterranean soils. In addition, analysis of the sensitivity toward its biotic parameters shows that the model is far more sensitive to some parameters, i.e., the microbial maintenance energy and the probability of random microbial death, than to others. These results suggest that, in the future, research should focus on securing better measurements of these parameters, on environmental determinants of the switch from active to dormant states, and on the causes of random cell death in soil ecosystems. Highlights ► The individual-based INDISIM-SOM model is far more sensitive to some parameters than to others. ► Key parameters for the evolution of C and N are microbial maintenance, energy, and death probability. ► The nitrification rate, in particular, appears highly affected by the death probability. ► The sensitivity analysis indicates what simplification of the model is possible. ► It also shows which parameters need to be evaluated with more accuracy than is currently achievable.