Different welfare indicators were studied in three patients with psychomotor alterations and in two horses throughout 9–10 equine assisted therapy sessions in each patient. In horses, heart and respiratory rates, blood pressure, temperature and behavioral signs were studied. In patients, heart rate, oxygen saturation, temperature, sleep quality, psychomotor and emotional parameters were analyzed. Data collection was recorded in the anticipatory phase (15 min before the start of the session), two interaction phases (after 30 min of horse-patient interaction on the ground and on horseback, respectively) and the recovery phase (15 min after the end of the session). During the anticipatory phase, most of physiological parameters of patients and horses and the stress behavioral signs of horses increased, followed by a relaxing phase during the horse-patient interaction on the ground. In horse-patient riding phase the heart and respiratory rates of the horses again increased. These results showed that the horses did not seem to suffer stress attributable to the therapy sessions, but only an increase in their parameters associated with activity and external stimuli. The patients improved their gross and fine motor skills, their cognitive and perceptual-sensitive parameters and it led to an improvement in the life quality of their families.