Pseudomonas aeruginosa is a versatile opportunistic human pathogen associated with acute and chronic infections, particularly affecting immunocompromised individuals, including those with cystic fibrosis (CF). The bacterium's ability to thrive under diverse environmental conditions, such as oxygen limitation in the mucus of CF patients, is central to its pathogenicity and a key contributor to persistence in hostile settings. Under anaerobic conditions and the absence of other energy-generating systems, pyruvate fermentation serves as an alternative strategy ensuring long-term survival and basal metabolism. In these growth-limiting, nutrient-deficient conditions, the universal stress protein UspK was found to be highly upregulated. This study investigates the role of UspK in facilitating adaptation to anaerobic stress, revealing a significantly decreased anaerobic survival rate of the UspK mutant. Upon switching to pyruvate fermentation, we observed alterations in LPS levels and a significant increase in AMP levels. Further analysis showed that UspK displays a nucleotide-binding motif capable of binding AMP, suggesting high AMP levels may act as a signal for starvation beyond stringent response. Supported by phenotypic analysis, our results highlight the critical role of UspK in anaerobic stress adaptation via pyruvate fermentation and survival in such famine conditions. This study provides new insights into stress response and niche adaptation of P. aeruginosa, which are crucial for targeting chronic infections.