Background: Yogic practices are known to affect the cardiac, respiratory and mental status of people. Objective: To investigate if the regularly supervised training of pranayama and meditation affects the basic cardio-respiratory parameters and short-term-memory (STM) of mentally challenged young adults. Material and methods: 80 mentally challenged young adults attending a special school were randomly divided into the control group and Yoga group. Yoga group performed Naadishodhan, Kapalbhati pranayama and Aum Chanting under total supervision for 30 min daily for 3 weeks, except on Sundays. Control group was involved with the regular school curriculum. The parameters were measured twice, before (baseline) and after (follow-up) the study period. STM was evaluated under two subcategories, first by the ability to repeat the numbers in reverse order and second, repeating the words in the same order. Respiratory rate, pulse, systolic and diastolic blood pressures were measured as cardio-respiratory parameters. Results: Both groups had similar baseline scores. At follow-up, highly significant improvements were observed in Yoga-group as compared to control. In the Yoga-group scores of both the sub-categories of STM were higher, respiratory-rate and heart-rate were lower but was within normal range. However, both systolic and diastolic blood pressures of Yoga group showed no changes as compared to control. Conclusion: The pranayama and meditation has beneficial influences on heart rate, breathing rate and STM of mentally-challenged people.