Abstract Background Recent studies have demonstrated the pivotal implications of the locus coeruleus (LC) and in the early phase of Alzheimer’s disease (AD). However, the effects of apolipoprotein E4(APOE4) carrier status on the LC functional connectivity (FC) in preclinical AD remain elusive. We aimed to demonstrate disparities in LC FC in preclinical AD with regard to APOE4 carrier status. Methods A total of 112 patients with who were amyloid beta (Aβ) positive([18F] flutemetamol +) were recruited in the study, and they all had normal cognition. Seed to voxel analysis was conducted to measure LC FC differences between APOE4 non‐carrier and carrier. In addition, group by amyloid beta (Aβ) interactive effects on FC values were analyzed with a general linear model. Result The LC FC with intracalcarine cortex, lingual gyrus, occipital fusiform gyrus of the both hemispheres was reduced in APOE4 carrier. Moreover, there was a statistically significant group by regional standardized uptake value ratio interactions in LC FC with frontal, occipital cortices, the precuneus and the cerebellum. Conclusion The aforementioned findings suggest that there are differential patterns of LC FC in APOE4 non‐carrier and carrier with preclinical AD, which interact with regional Aβ deposition.