This study was designed to determine whether yoga might alleviate symptoms of pain, sleep disturbance, anxiety, and depression in children with cystic fibrosis (CF). CF is the most common genetic, life-limiting chronic disease among Caucasian populations. It primarily affects the lungs but also many other secretory organs and consequently leads to significant morbidities. Research has shown that children with CF have significantly increased depression, anxiety, and pain compared to their healthy counterparts. Subjects participated in six one-on-one sessions over a 10-week period with a certified instructor who designed each yoga practice based on a preestablished list of 30 yoga asanas. Questionnaires evaluating pain, sleep disturbance, sustained anxiety, immediate anxiety, and depression were administered. Differences between premeasures and postmeasures were evaluated using a two-sided test. Twenty subjects were assessed (12 females/8 males), median age of 11 (7-20) years. Mean immediate anxiety scores decreased (before session to after session 29 to 23.6, respectively, p < 0.001). Joint pain improved (3.25 to 3.65, p = 0.028). CFQ-R emotion subscale improved from 79.2 to 85 (p = 0.073), and the respiratory subscale improved from 66.7 to 79.2 (p = 0.076). Other results were less notable. We conclude that yoga may reduce immediate anxiety and joint pain in patients with CF.