Sepsis is a condition that results from a harmful or damaging host response to infection with organ dysfunction. Every year about 20 million people are dead owing to sepsis and its mortality rates is as high as 20%. However, no studies have been carried out to investigate sepsis from the system biology point of view, since previous studies mainly focused on individual genes in sepsis, ignoring the interactions and associations among the genes and transcripts. Here, we explored the expression alteration of both mRNAs and long non-coding RNAs (lncRNAs) in sepsis on a genome-wide scale, on the basis of six microarray datasets. Co-expression networks were conducted to identify mRNA and lncRNA modules, respectively. Comparing with the normal modules, we observed that the mRNA/lncRNA members in sepsis module tend to express in a homogeneous way, a majority of them are expressed in the same direction. Furthermore, consistent modules among diverse datasets were determined with 20 common mRNA members and two lncRNAs, CHRM3-AS2 and PRKCQ-AS1, which are expected to be candidate regulators of sepsis. Our results reveal that the up-regulated common mRNAs are mainly involved in the processes of neutrophil mediated immunity, while the down-regulated mRNAs and lncRNAs are significantly overrepresented in T-cell mediated immunity functions. This study concentrated on co-expression pattern of mRNAs and lncRNAs in sepsis to provide a novel perspective and insight into sepsis transcriptome, which may facilitate the exploration of candidate therapeutic targets and molecular biomarkers for sepsis.