The lungs are normal at birth, but breathing problems can develop at any time afterward. Thick secretions eventually block the small airways, which leads to inflammation and thickening of their walls. As larger airways fill with secretions, areas of the lung collapse and contract (a condition called atelectasis), and the lymph nodes enlarge. All these changes make breathing increasingly difficult and reduce the lungs' ability to transfer oxygen to the blood. Respiratory tract infections occur because of bacterial growth in the bronchial secretions and walls of the airways.

The blockage of pancreatic ducts and intestinal glands leads to digestive problems, including poor absorption of fats, proteins, and vitamins. This, in turn, can lead to nutritional deficiencies, and slower than expected growth. Some people may have episodes of intestinal obstruction when abnormal stool contents block the bowel.

About 15 to 20% of newborns who have cystic fibrosis have meconium ileus, a serious obstruction of the small intestine. Meconium ileus is sometimes complicated by a twisting of the intestine on itself (volvulus) or incomplete development of the intestine. Newborns who have meconium ileus almost always develop other symptoms of cystic fibrosis later. Meconium can also temporarily obstruct the large intestine in some newborns with cystic fibrosis, so that a bowel movement may not occur in these newborns until 1 to 2 days after birth.

The first symptom of cystic fibrosis in an infant who does not have meconium ileus is often a delay in regaining birth weight or poor weight gain at 4 to 6 weeks of age. Inadequate amounts of pancreatic enzymes, which are essential for proper digestion of fats and proteins, lead to poor digestion in most infants with cystic fibrosis. The infant has frequent, bulky, foul-smelling, oily stools and may have a distended abdomen and small muscles. Weight gain is slow despite a normal or large appetite.

About half the children with cystic fibrosis are first taken to the doctor because of frequent coughing, wheezing, and respiratory tract infections. Coughing, the most noticeable symptom, is often accompanied by gagging, vomiting, and disturbed sleep. As the disease progresses, the chest becomes barrel-shaped, and insufficient oxygen may make the fingers clubbed and the nail beds bluish. Polyps may form in the nose. The sinuses may fill with thick secretions, leading to chronic or recurrent sinus infections.

When a child or adult with cystic fibrosis sweats excessively in hot weather or because of a fever, dehydration may result because of the increased loss of salt and water. A parent may notice the formation of salt crystals or even a salty taste on the child's skin.

Adolescents often have slowed growth, delayed puberty, and declining physical endurance. As the disease progresses, lung infection becomes a major problem. Recurrent bronchitis and pneumonia gradually destroy the lungs.