BackgroundAcute diarrhea with fever can potentially represent a more severe form of the disease compared to non-febrile diarrhea. This study was to investigate the epidemiological characteristics and enteric pathogen composition of febrile-diarrheal patients, and to explore factors including pathogens associated with fever by age group.MethodsA nationwide surveillance study of acute diarrheal patients of all ages was conducted in 217 sentinel hospitals from 31 provinces (autonomous regions or municipalities) in China between 2011 and 2020. Seventeen diarrhea-related pathogens, including seven viruses and ten bacteria, were investigated and their association with occurrence of fever symptoms was assessed using multivariate logistic analysis.ResultsA total of 146,296 patients with acute diarrhea (18.6% with fever) were tested. Th diarrheal children below 5 years had the highest frequency of fever (24.2%), and related to significantly higher prevalence of viral enteropathogens (40.2%) as compared with other age groups (P< 0.001). Within each age group, the febrile-diarrheal patients were associated with a significantly higher prevalence of bacterial pathogens than afebrile-diarrheal patients (allP< 0.01). There was discrepancy when each pathogen was compared, i.e., nontyphoidalSalmonella(NTS) was overrepresented in febrile vs non-febrile patients of all age groups, while the febrile vs non-febrile difference for diarrheagenicEscherichia coli(DEC) was only significant for adult groups. The multivariate analysis revealed significant association between fever and infection with rotavirus A among children [odds ratio (OR) = 1.60], for DEC in adult groups (OR= 1.64), for NTS in both children (OR= 2.95) and adults (OR= 3.59).ConclusionsThere are significant discrepancy of the infected enteric pathogens in patients with acute diarrhea with fever between age groups, and it is valuable for priority detection of NTS and rotavirus A in patients with children < 5 years old and NTS and DEC in adult patients. The results may be useful in identifying dominant pathogen candidates for the application of diagnostic assays and prevention control.Graphical AbstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s40249-023-01108-w.