The nature and origin of the generalized anomeric effect is investigated with energy components and information-theoretic quantities from density functional reactivity theory. Forty-five systems with the general formula of R-1-X-CH2-Y-R-2 were examined, where R-1 and R-2 are functional groups and X and Y as electronegative heteroatoms. Our results show that in most cases the effect is valid, and the dominant contribution for the validity of the effect is from the electrostatic interaction. Other contributions such as steric and hyperconjugation play minor but indispensable roles. Its relationship with the conventional anomeric effect is compared and discussed. (C) 2017 Elsevier B.V. All rights reserved.