Objective To explore the impact of fluid therapy through enteral feeding tube on energy target achievement and glycemic variability (GV) in neurosurgical critically ill patients during early enteral nutrition (EN). Methods A multicenter prospective cohort study was conducted in four tertiary hospitals in Shanghai from January to December 2023. A total of 136 neurosurgical critically ill patients were divided into two groups of 68, the control group who only received EN and the exposure group who received 500 mL of fluid through feeding tube before routine EN. The differences in energy target achievement within 3 days of initiating EN, GV, gastrointestinal tolerance, and EN time were compared between the two groups. Results A total of 65 patients in the control group and 61 in the exposure group completed the study. The exposure group had significantly lower energy target achievement rate, higher GV, and shorter EN time compared to the control group (all P<0.05). There was no significant difference in gastrointestinal tolerance between the two groups (P>0.05).Conclusion Fluid therapy given through enteral feeding tube may impact energy target achievement rate and GV in neurosurgical critically ill patients during early EN, so it is not recommended.