This chapter outlines the experimental methods for inducing Depression-like behavior in mice by separating group-housed mice to individual housing. This is a model of loneliness in mice. Loneliness-induced depression is measured using the forced swim test (FST) and tail suspension test (TST). The first part of the chapter describes the methods for inducing separation-induced depression. It summarizes the experimental protocols including behavioral testing of the animals. The second part describes some of the issues to be concerned within this paradigm. An up-to-date collection of protocols and procedures for troubleshooting are provided.