The objective of this study was to validate and test the efficacy of a 16-week tele-yoga intervention for perceived stress, anxiety, depression, and insomnia in individuals who had had COVID-19 infection in the previous year, and had reported moderately high levels of psychological stress (PSS ≥14). 25 and 50-min versions of the program were developed. They were then validated using Lawshe’s content validity ratio after obtaining feedback from 20 yoga therapy experts. The safety and efficacy of the two programs were subsequently tested in a prospective, multicenter, open-label single-arm study. Eighty-six adults (18 male, 68 female) were recruited from two tertiary mental healthcare institutions, 48 in NIMHANS, Bengaluru; and 38 in SCARF, Chennai. Participants were assessed at weeks zero, 4, and 16 using validated tools. Data were analyzed using a Mixed Model, Intention to Treat approach. After week 16, 31 subjects remained in the trial and continued to practice yoga without any side effects. Subjects who adhered in the trial had significantly higher levels of baseline anxiety and depression as compared to subjects who dropped out. Results at week 4 included significant reductions in levels of perceived stress, anxiety, and insomnia; improvements were maintained at week 16. Correlations between number of yoga sessions and post-intervention PSS scores were negative (r = −0.49), and significant (p< 0.05). Both tele-yoga programs proved safe, useful tools to counteract perceived stress, anxiety and insomnia. Future trials should explore the utility of tele-yoga as a tool to enhance well-being and manage stress.