While carbonate reservoirs are recognized to be weakly-to-moderately oil-wet at the core-scale, pore-scale wettability distributions remain poorly understood. In particular, the wetting state of micropores (pores <5 µm in radius) is crucial for assessing multi-phase flow processes, as microporosity can determine overall pore-space connectivity. While oil-wet micropores are plausible, it is unclear how this may have occurred without invoking excessively high capillary pressures. Here, we develop a novel mechanistic wettability alteration scenario that evolves during primary drainage, involving the release of small polar non-hydrocarbon compounds from the oil-phase into the water-phase. We implement a diffusion/adsorption model for these compounds that triggers a wettability alteration from initially water-wet to intermediate–wet conditions. This mechanism is incorporated in a quasi-static pore-network model to which we add a notional time-dependency of the quasi-static invasion percolation mechanism. The model qualitatively reproduces experimental observations where an early rapid wettability alteration involving these small polar species occurred during primary drainage. Interestingly, we could invoke clear differences in the primary drainage patterns by varying both the extent of wettability alteration and the balance between the processes of oil invasion and wetting change. Combined, these parameters dictate the initial water saturation for waterflooding. Indeed, under conditions where oil invasion is slow compared to a fast and relatively strong wetting change, the model results in significant non-zero water saturations. However, for relatively fast oil invasion or small wetting changes, the model allows higher oil saturations at fixed maximum capillary pressures, and invasion of micropores at moderate capillary pressures.