As adhesives containing hydrophilic/acidic resin components are vulnerable to water movement after polymerization, this study tested the hypothesis that coupling of a single-bottle adhesive (OptiBond Solo Plus) to self/dual-cured composites is compromised by adhesive permeability, even with the adjunctive use of chemical co-initiators. Two versions of chemical co-initiators (activators) were investigated: the proprietary resin-containing OptiBond Solo Plus Activator (A), and a resin-free solution of 2% benzene sulphinic acid sodium salt in ethanol (B). For microtensile bond testing, hydrated (H) or dehydrated (D) bonded human dentin were coupled to a dual-cured composite (Bis-Core) under light- (L) or self-activation (C) mode. A delayed light-activation mode (DL) was also employed to simulate the slower rate of polymerization of self-cured composites but without the influence from adverse chemical interaction. Nine groups were tested: 1) L-H (control); 2) DL-H; 3) DL-D; 4) C-H; 5) C-D; 6) CA-H; 7) CA-D; 8) CB-H; and 9) CB-D. For transmission electron microscopy, a light-cured and an experimental self-cured composite of the same composition were used for the nine groups. Only the bond strength results of the experimental groups DL-D (Group 3) and CB-D (Group 9) were not significantly different from the control group L-H (p > 0.05). TEM revealed the presence of discrete silver-filled water blisters along the adhesive-composite interface in groups 2, 6, and 8, and within the composite in group 4. Adverse chemical interaction in groups 4 and 5 resulted in the observation of a line of silver deposits along the adhesive composite interface. The coupling of composites after prolonged contact with hydrated dentin bonded with OptiBond Solo Plus is affected by the intrinsic permeability of the adhesive. The adjunctive use of the Activator is only slightly effective in improving the coupling of this adhesive with self/dual-cured composites. Although the use of resin-free benzene sulphinic acid sodium salt solution completely eliminates the adverse chemical interaction, the inherent permeability of the polymerized adhesive precludes optimal coupling of self/dual-cured composites to bonded hydrated dentin.