Low salinity waterflooding is a low-cost method of enhancing oil recovery although, no consistent concept has been established explaining why some oil-fields show an increase in oil production when the salinity of the injected brine is reduced, while others do not. Various studies were conducted investigating the underlying mechanisms of the ‘low salinity effect’ using different crude oil, brine and rock compositions. Core floods of sandstone rock and analyses of molecular interactions using model systems indicate that clay content may play a dominant role. However, the spatial configuration of the sheet-like clay particles, which may vary from rock to rock, complicate comparisons of these model scenarios with reality. In the present study, we report the development of a pre-screening method using Atomic Force Microscopy (AFM) to assess rock-fluid interactions, which has previously only been used either on artificial model systems or minerals from crushed rock, by exploring the capability to operate in-situ in complex rock without crushing. The orientation of clay particles within a pore of an outcrop sandstone, Bandera Brown, was investigated with AFM and these particles were further assessed for changes in adhesion in brines of differing salinity. The results show a decrease in adhesions between CH3-functionalised AFM tips and the rock surface in low salinity brine, predominantly at the clay edges. This demonstrates that the edges of the clay particles, which may pin the oil phase after wettability alteration and therewith prevent oil from getting produced, lose this capacity when exposed to low salinity brine.