Background: Nasal irrigations with antibiotics are used to eradicate Pseudomonas aeruginosa from the upper airways in patients with cystic fibrosis (CF) and thereby avoid lung colonisations; nevertheless, the efficacy is uncertain. Methodology: The aim of this study was to investigate the accessibility and durability of solutions in the sinuses before and after sinus surgery. The participants irrigated their noses with radioactively marked saline and were evaluated using a dynamic SPECT/ CT scan. The preoperative and postoperative (after 30 days) examinations were compared. Results: Twelve CF patients were included. In 10 out of the 24 scanned maxillary sinuses an improvement was seen postoperatively compared with the preoperative fluid volume. Notably, in 7 out of the 24 sinuses the mucosa was so swollen postoperatively that no fluid was detected. Ten patients had developed their frontal sinuses. We observed no fluid in the frontal or sphenoid sinuses, neither before nor after surgery. At best, a mean of 23% of the maxillary sinuses were filled with fluid; thus, all sinuses had postoperatively areas of the mucosa that did not have contact with the fluid. A mean of 76% of the initial volume was present after 30 min in the maxillary sinuses. Conclusion: Fluid-depositing using nasal irrigation will not sufficiently or not at all get in contact with all the sinus mucosa despite of sinus surgery. Thus, the efficacy of topical deposition of antibiotics is presumably reduced.