Introduction: Early prediction of the Systemic Inflammatory Response Syndrome (SIRS) by assessing clinical manifestations, related and risk factors is a key precursor affecting the development of sepsis in newborns. Aims: The aim of the review study was to analyze Czech and foreign literary sources and professional periodicals to obtain a relevant comprehensive overview of the possibilities for assessment of clinical and laboratory indicators SIRS and sepsis in newborns. Methods: Literature review. Results: There are many clinical signs of neonatal sepsis. Initially they are very often non-specific, variable, in some cases discrete to silent. Laboratory monitoring of inflammatory markers is an accurate indicator of neonatal sepsis. However, the accuracy of laboratory diagnosis depends on the level of advanced disease. At present, invasive methods of detecting inflammatory markers for diagnosis of sepsis in combination with assessment of somatic and neurological manifestations of newborn are preferred in clinical practice. Conclusion: Finding new possibilities in the diagnosis of sepsis predictors and validate their reliability is an important step in supporting safe and effective care of newborns.