Background <p>Hyperuricemia is a widely prevalent health disorder that impacts a substantial population globally and is linked to several chronic diseases. The relationship between hyperuricemia and inflammation, in light of inflammatory indices MLR, NLR, and PLR, in the general population is not well-established. The main objective of this study is to evaluate the potential association between MLR, NLR, and PLR with hyperuricemia in the Saudi population.</p> Methods <p>The laboratory data of the studied subjects were collected from Al Borg Diagnostics. The subjects were categorized into two groups based on their uric acid (UA) levels: normourcemic and hyperuricemic. The potential relationship between UA levels and MLR, NLR, and PLR was investigated. In addition, risk measures and the diagnostic performance of MLR, NLR, and PLR for hyperuricemia were analyzed.</p> Results <p>Our observations showed that the MLR was significantly increased, while the PLR was significantly decreased in the hyperurcemic subjects. NLR was slightly elevated in only female subjects with hyperuricemia. Decreased PLR (PR = 6.2156, 95% CI 3.19–12.07, p &lt; 0.0001) and elevated MLR (PR = 1.23, 95% CI 1.05–1.43, p &lt; 0.0001) were associated with an increased risk of hyperuricemia in the studied population. In addition, receiver operating characteristic curves analysis showed that both PLR and MLR, but not NLR, were better than CRP in discriminating hyperuricemic individuals.</p> Conclusion <p>This study showed a significant association between hyperuricemia and elevated MLR and reduced PLR in the Saudi population. Both inflammatory markers may be used in the management of hyperuricemia in Saudi adults. Further studies are needed to confirm our findings in longitudinal studies and in other ethnic groups.</p>