Cystic fibrosis (CF) is commonly associated with polymicrobial infections, with Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans being among the most frequent species isolated from sputum samples. To adapt and survive in this complex and competitive environment, P. aeruginosa must precisely tune its gene expression and small RNAs (sRNAs) represent a fine way to shape its physiology upon exposure to stress conditions. Through RNA-seq analysis of samples from an in vitro continuous-flow system that recapitulates CF-associated polymicrobial infections with high fidelity and stability, I analysed highly expressed intergenic regions. This led to the identification of several sRNA candidates that may contribute to the regulation of P. aeruginosa physiology in the CF context. Among them, a conserved sRNA in Pseudomonas spp, was found to positively influence OprE porin abundance. OprE, one of the most numerous porins, primarily serves as an entry point for carboxylate-containing nutrients and may confer a competitive advantage when overexpressed. Another sRNA is transcribed from the intergenic region flanking the aceA gene which is essential for acetate utilization. Initial findings indicate that overexpression of the sRNA prevents growth on acetate as the sole carbon source. This preliminary data indicates a possible role in acetate metabolism regulation, crucial for P. aeruginosa as it utilizes acetate, abundant in airways secretions and acetoin, a by-product of S. aureus metabolism which has been shown to represent a cooperative interaction between the two species. Taken together, these results suggest multiple sRNA-mediated mechanisms through which P. aeruginosa modulates its metabolism in CF-related polymicrobial infections.