Objective: To study the prevalence of depression among caregivers of children with cystic fibrosis and its impact on the health and well being of these children. Methods: This cross-sectional study was conducted in a tertiary care hospital from September 2015 through August 2016. Forty one parents of children receiving treatment at the Cystic fibrosis (CF) clinic were approached to be part of the study. Six families declined the request resulting in 85% recruitment rate. The Centre for Epidemiological Studies Depression Scale (CES-D) was used to assess depression score among caregivers. The CES-D provides clinical cut-off scores of ≥16 that help in identifying persons at risk for depression. CES-D was completed by the parent closely associated with care of the affected child. Main outcome measure was to find the number of caregivers of patients who has score of ≥16 on CES-D scale, and its effect on growth and respiratory exacerbations of the affected child. Results: A total of 23 fathers and 12 mothers participated in the study. The mean age of male and female caregivers was 30.9 ± 5.4 and 27.8 ± 4.7 y respectively. Eighteen (51.4%) caregivers scored above the clinical cut-off on the CES-D in the index study with mean score of 22.0 ± 4.0. The mean CES-D score among non-depressive caregivers was 7.76 ± 4.2. Significant negative association was found between parental depression and child's health. Children with high parental CES-D score suffered significantly more respiratory exacerbations (3.83 ± 1.2 episodes) in last six months than parents with low CES-D score (2.18 ± 1.28 episodes) (p value = 0.00). Similarly, stunting was more commonly seen in patients with high caregiver CES-D score (15 vs. 7; P value = 0.01). Conclusions: A very high prevalence of caregiver depression was found in cystic fibrosis, which negatively impacted care and well being of the affected patients. Depression was more common in families with poor economic and education level.