Work-related stress and associated illness and burnout is rising in western society, with now as much as almost a quarter of European and half of USA’s employees estimated to be at the point of burnout. Mindfulness meditation, yoga, and physical exercise have all shown beneficial effects for work-related stress and illness. This proof of concept study assessed the feasibility, acceptability, and preliminary effects of the newly developed Mindful2Work training, a combination of physical exercise, restorative yoga, and mindfulness meditations, delivered in six weekly group sessions plus a follow-up session. Participants (n = 26, four males), referred by company doctors with (work-related) stress and burnout complaints, completed measurements pre and post the intervention, as well as at 6-week (FU1) and 6-month (FU2) follow-up. Results showed very high feasibility and acceptability of the Mindful2Work training. The training and trainers were rated with an 8.1 and 8.4 on a 1–10 scale, respectively, and training dropout rate was zero. Significant improvements with (very) large effect sizes were demonstrated for the primary outcome measures of physical and mental workability, and for anxiety, depression, stress, sleep quality, positive and negative affect, which remained (very) large and mostly increased further over time. Risk for long-term dropout from work (checklist individual strength [CIS]) was 92 % at pre-test, reduced to 67 % at post-test, to 44 % at FU1, and 35 % at FU2, whereas employees worked (RTWI) 65 % of their contract hours per week at pre-test, which increased to 73 % at post-test, 81 % at FU1 and 93 % at FU2. Intensity of home practice or number of attended sessions were not related to training effects. To conclude, the newly developed Mindful2Work training seems very feasible, and acceptable, and although no control group was included, the large effects of Mindful2Work are highly promising.