DeSales High School places a strong emphasis on the faith-component of its education, presenting a wide array of opportunities for spiritual growth. For its work, the school has been recognized by the Archdiocese of Louisville with the Thomas Duerr Award for excellence in catechesis.
A program of retreats is provided for all students at DeSales. Freshmen and sophomore "Days of Renewal" are mandatory for all students, while the junior and senior retreats are optional. Class Masses and all-school Masses are held throughout the year on Feast Days and Holy Days of Obligation. DeSales students and staff actively participate as servers, Eucharistic ministers, and ministers of hospitality.
The Joseph of Arimathea Society at DeSales provides a greater sense of dignity and reverence to the funerals of the poor and indigent. The Society is supported by the Jefferson County Coroner's office and takes place at the River Valley Cemetery. Students serve as pallbearers and assist in a prayer service.
Students from DeSales are also encouraged to attend the annual National Catholic Youth Conference (NCYC) either through DeSales or through their parish youth groups.