Life-threatening dysfunction of organs, known as sepsis, is caused by an imbalanced response of host to infection. In this work, an efficient algorithm is proposed to address vital biomarkers for identification of sepsis using immunerelated differential expression genes. A total of 16 gene datasets are processed for the extraction of a gene intersection between different gene datasets and the immune-related gene group, which improve the generalization of the final detection algorithm due to diversity of the input data. A novel gene selection method using sequential forward gene selection, machine learning, and ranked genes based on their importance calculated by a random forest model. A subset of 36 potential immune-related genes, which are identified as the biomarkers from 560 input genes, show an efficiency of the proposed gene selection algorithm. The biomarkers are validated the performance using various machine learning and deep learning related to sepsis diagnosis. The highest statistical performance is shown for the random forest model using the biomarkers as the input with an accuracy of 96.83%, sensitivity of 98.86%, specificity of 86.70%, and AUC of 98.67%. The proposed detection algorithm includes a random forest model and 36 biomarkers, which is simple, effective, and reliable for the applications in clinic environments.