Candida albicans is frequently co-isolated with the Gram-negative bacterium, Pseudomonas aeruginosa. In vitro, the interaction is complex, with both species influencing each other. Not only does the bacterium kill hyphal cells of C. albicans through physical interaction, it also affects C. albicans biofilm formation and morphogenesis, through various secreted factors and cell wall components. The present study sought to expand the current knowledge regarding the interaction between C. albicans and P. aeruginosa, using transcriptome analyses of early static biofilms. Under these conditions, a total of 2,537 open reading frames (approximately 40% of the C. albicans transcriptome) was differentially regulated in the presence of P. aeruginosa. Upon deeper analyses it became evident that the response of C. albicans toward P. aeruginosa was dominated by a response to hypoxia, and included those associated with stress as well as iron and zinc homeostasis. These conditions may also lead to the observed differential regulation of genes associated with cell membrane synthesis, morphology, biofilm formation and phenotypic switching. Thus, C. albicans in polymicrobial biofilms with P. aeruginosa have unique transcriptional profiles that may influence commensalism as well as pathogenesis.