This paper studies the effects of nano-TiO2 in CO2 sequestration of hardened cement paste depending on the water-to-cement ratio (w/c) and the pore structure. Twelve cement paste mixtures were prepared with four different percentages of nano-TiO2 (0%, 0.5%, 1%, 2%) and three w/c (0.45, 0.50, 0.55). Samples were exposed for 24 h to a CO2 environment at two different ages (14 and 28 days). Thermogravimetric analysis and 3D X-Ray scans of the pore structure were performed on exposed and unexposed samples. Results showed that nano-TiO2 produces an improvement in the CO2 uptake until a certain percentage. This maximum percentage depends on exposure age and w/c. Nano-TiO2 produces a reduction in porosity and an increment of calcium hydroxide (CH) reactivity, which have opposite effects on CO2 uptake. These two competing mechanisms may explain why nano-TiO2 can be beneficial or detrimental for the CO2 uptake as a function of w/c ratio and age.