| Summary: | (1) <b>Background</b>: We aim to identify clinical and laboratorial parameters to distinguish <i>Kingella kingae</i> from pyogenic septic arthritis (SA). (2) <b>Methods</b>: A longitudinal, observational, single-centre study of children < 5 years old with microbiological positive SA admitted to a paediatric hospital from 2013–2020 was performed. Clinical and laboratorial data at admission and at 48 h, as well as on treatment and evolution, were obtained. (3) <b>Results</b>: We found a total of 75 children, 44 with <i>K. kingae</i> and 31 with pyogenic infections (mostly MSSA, <i>S. pneumoniae</i> and <i>S. pyogenes)</i>. <i>K. kingae</i> affected younger children with low or absent fever, low inflammatory markers and a favourable prognosis. In the univariate analyses, fever, septic look, CRP and ESR at admission and CRP at 48 h were significantly lower in <i>K. kingae</i> SA. In the multivariate analyses, age > 6 months ≤ 2 years, apyrexy and CRP ≤ 100 mg/L were significative, with an overall predictive positive value of 86.5%, and 88.4% for <i>K. kingae</i>. For this model, ROC curves were capable of differentiating (AUC 0.861, 95% CI 0.767–0.955) <i>K. kingae</i> SA from typical pathogens. (4) <b>Conclusions</b>: Age > 6 months ≤ 2 years, apyrexy and PCR ≤ 100 mg/L were the main predictive factors to distinguish <i>K. kingae</i> from pyogenic SA < 5 years. These data need to be validated in a larger study.
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