People with disabilities due to genetic origin often present high levels of stress: non-pharmacological interventions such as Equine-Assisted Interventions (EAI) may be a useful strategy. The objective of this pilot study was to evaluate stress levels in two participants with 22q11.2 deletion syndrome diagnosis, immediately after carrying out the EAI. A single case experimental design methodology was chosen due to the small sample size. Two participants with 22q11.2 Deletion Syndrome, a rare disease, with different comorbidities were included. The present study considered the EAI as the independent variable while the Heart Rate Variability (HRV) represented the dependent one, as HRV is considered an indicator of stress level. Measurements were performed before and after carrying out the interventions. The results showed an HRV increase in one of the participants and an increase in the arousal level evidenced by a decrease in his HRV. After having carried out the program, EAI seems to cause an impact on the activation level of the participants depending on the typology and nature of the intervention. However, these results should be treated with caution due to the small sample size. This study is a pilot to test the feasibility of the proposed interventions on the variable under study.