This open access book constitutes the proceedings of the 22nd International Conference on Foundations of Software Science and Computational Structures, FOSSACS 2019, which took place in Prague, Czech Republic, in April 2019, held as part of the European Joint Conference on Theory and Practice of Software, ETAPS 2019. The 29 papers presented in this volume were carefully reviewed and selected from 85 submissions. They deal with foundational research with a clear significance for software science.