Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percent solids and protein content are all greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis (CF), a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibited heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. These results highlight the dramatic biophysical properties of COVID-19 respiratory secretions and suggest that DNA and hyaluronan may be viable therapeutic targets in COVID-19 infection.