<p>Religious/spiritual struggles arise when some aspects of religious/spiritual belief, practice, or experience become a focus of negative thoughts, emotions, concerns or conflict. Sanctification refers to the degree to which an aspect of life is perceived (a) as a manifestation of God or Higher Powers (i.e., theistic sanctification) and/or (b) as imbued with sacred qualities (i.e., non-theistic sanctification). This is the first investigation we know to target the interplay of individuals’ religious and spiritual struggles concerning their sex life/activity and the sanctification of their sexual relationship with their spouse/partner in predicting sexual satisfaction. Participants were 309 Israeli Jewish (<i>M</i> age = 34.5, 74% women) who were married (91%) or in a stable romantic relationship, reported some degree of religious or spiritual proclivity, and completed self-report measures via an online survey. Sexual satisfaction was associated with lower religious/spiritual struggles (<i>r</i> = −0.21, <i>p</i> &lt; 0.01) and greater non-theistic sanctification of relational sexuality (<i>r</i> = 0.22, <i>p</i> &lt; 0.01), but was unrelated to theistic sanctification. Furthermore, only non-theistic sanctification moderated the association between religious/spiritual struggles and sexual satisfaction (<i>b</i> = 0.10, <i>t</i> = 2.23, <i>p</i> &lt; 0.05), such that as the level of non-theistic sanctification increases, the negative relationship between religious/spiritual struggles and sexual satisfaction decreases. These findings suggest that religious/spiritual struggles with sexual life/activity may constitute a risk factor for lower sexual satisfaction, and non-theistic sanctification of relational sexuality may buffer individuals from such a risk.</p>