Purpose: To assess the impact of human crystalline lens opacification and yellowing, similar to that observed in patients with cataracts, on retinal vessel blood oxygen saturation measurements using custom manufactured soft contact lenses. Methods: Ten healthy, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intra-ocular pressure, pupil dilation and retinal vessel oximetry using dual-wavelength photography (Oximetry Module, Imedos Systems). To simulate lens changes, three different contact lenses were inserted, one to simulate opacities followed by two more lenses to simulate different levels of lens yellowing (Cantor & Nissel). Results: The measurements obtained showed an opposite change in arterial and venous oxygen saturation and optical density ratio across conditions, resulting in a statistically significant difference in arterial minus venous oxygen saturation value (p = 0.003). However, this difference was only significant for the 'opacity' condition but not for the 'yellowing' conditions. Conclusion: Lenticular changes such as cataracts can impact on spectrophotometric analysis in particular dual-wavelength retinal vessel oximetry. Hence, lenticular assessment and cataract grading should be considered when assessing elderly individuals and patient groups developing cataract earlier in life such as those suffering from diabetes mellitus.