Moraxella catarrhalis is a human host-adapted, opportunistic bacterial pathogen of the respiratory mucosa. Although asymptomatic colonization of the nasopharynx is common, M. catarrhalis can ascend into the middle ear where it is a prevalent causative agent of otitis media in children, or enter the lower respiratory tract where it is associated with acute exacerbations of chronic obstructive pulmonary disease in adults. Phase variation is the high frequency, random, reversible switching of gene expression that allows bacteria to adapt to different host microenvironments and evade host defences, and is most commonly mediated by repetitive tracts of DNA. Bioinformatic analysis identified 17 unique DNA sequence repeat tracts that appeared to vary in size between five closed M. catarrhalis genomes. We investigated the six top candidates by enriching populations with single repeat units and show phase variation of uspA1, uspA2, mid/hag, a conserved hypothetical gene andmodO. We demonstrate that phase variation of uspA1 (from high to low expression) occurs during repeat exposure to human serum, while phase variation of uspA2 to a low expression variant similarly occurs over 72 hours of biofilm growth. We also identify and confirm the variable expression of two novel phase variable genes encoding a Type III DNA methyltransferase (ModO) and a conserved hypothetical gene (MC25239_RS00020). These data reveal the repertoire of phase variable genes mediated by simple sequence repeats in M. catarrhalis and indicate that phase variation occurs and correlates with altered gene expression under conditions mimicking human infection.