Development of goiter and hypothyroidism has been reported in patients with cystic fibrosis (CF) since the 1970s, especially when treated with iodine-based expectorants. With iodine-containing expectorants no longer in routine use, the prevalence of thyroid dysfunction in CF patients is unknown. This cross-sectional study assessed thyroid function status in a large cohort of CF patients. Sera from ambulatory subjects were obtained from an Institutional Review Board (IRB)-approved biorepository of patients seen at the Emory CF Center between January 1, 2011, and December 31, 2014. Sera from hospitalized subjects were obtained from banked specimens from an IRB-approved inpatient clinical trial. Demographics, forced expiratory volume in one second (FEV1), and medication use were assessed from medical records. Thyroid function tests were measured from the stored sera. Multivariate regression models assessed associations between covariates and thyrotropin (TSH), free thyroxine (fT4), and thyroid dysfunction risk. A total of 89 subjects (54% male, 91% white, Mage = 24.4 years, median FEV1 63%) were included in the analyses. One subject was on thyroid hormone replacement, 93% were on pancreatic enzyme replacement, and 68% received antibiotics within six months. None had computed tomography scans with intravenous contrast within six months. One patient had positive thyroid peroxidase (TPO) antibodies. Of the 87 subjects with measured TSH values, seven (8%) had abnormal levels (range 0.2-7.6 μIU/mL; one overt, four subclinical hypothyroidism, and two subclinical hyperthyroidism). Of the 56 subjects with measured fT4 values, 19 (34%) had slightly low levels (range 0.49-0.79 ng/dL; 17 isolated mild hypothyroxinemia). A positive correlation between age and body mass index (BMI; p < 0.001) and a negative correlation between age and FEV1 (p = 0.041) were seen. Age, sex, race/ethnicity, BMI, FEV1, hospitalization status, use of pancreatic enzyme or thyroid hormone replacement, recent antibiotic use, and TPO antibody positivity were not predictive of TSH, fT4, or thyroid dysfunction risk. Stratified analyses by hospitalization did not predict TSH or fT4. Although 24 (27%) of the patients had abnormal serum thyroid function tests, overt thyroid dysfunction was rare in this cohort of 89 patients with CF. The degree of hypothyroxinemia was marginal, likely due to nonthyroidal illness. There were no significant predictors of thyroid dysfunction.