Water interacts with collagen to alter the structure at the fibrillar scale and therefore the mechanical properties of collagen. Humectants or moisturizers also alter the mechanical properties and fibril structure. The nature of these interactions and relationship between the different additives is not well understood. Changes in collagen D-spacing in leather were measured by synchrotron based small angle X-ray scattering in samples stored at various relative humidities and treated with lanolin, fatliquor, urea, proline or paraffin. The D-spacing increased with rising humidity and with increasing lanolin or fatliquor content, but not with treatment with urea, proline or paraffin. Strength increased with the addition of lanolin. Lanolin and fatliquor were shown to act as humectants whereas the other components did not act in this way. The Hofmeister effect is shown not to be a factor in the change in D-spacing, since samples treated with either proline or urea exhibited the same behavior. Different agents used in leather treatment and skin care function by different mechanisms, with collagen water retention being important for some additives but not others.