Inquilinus limosus is an uncommon, poorly understood bacterium capable of infecting the respiratory tracts of people with cystic fibrosis. The transmission, clinical relevance and changes in antimicrobial resistance of I. limosus over time are unclear due to the low frequency of identification. We report three co-habiting brothers with cystic fibrosis who developed chronic I. limosus infection and document the clinical and microbiological features of the infections. Clinical evolution after Inquilinus infection varied but was associated with an initial decline in lung function. Familial clustering of this rare pathogen raises the possibility of cross-infection as a potential mechanism of transmission of Inquilinus between CF patients.