In general, studies of spirituality show positive associations with measures of well-being, but less is known about the possible role of mental distress in this association. Following the two-continua model of mental health, the current quantitative four-week follow-up study examines how spirituality is associated with well-being and mental distress. Spirituality is measured using the Spirituality Attitude and Interest List questionnaire (SAIL), well-being by the Dutch Mental Health Continuum-Short Form (MHCSF-SF), and mental distress by the Symptom Questionnaire (SQ-48). At baseline, 874 adults from the Netherlands and Belgium completed the online questionnaire; four weeks later, 560 participants completed the follow-up questionnaire. Multiple regression analyses showed that spirituality at baseline, and in particular the subscale on 'meaning in life,' predicted higher well-being scores at follow-up after adjustment for baseline well-being scores. Spirituality also predicted changes in mental distress scores, in particular on the subscales of trust and transcendent experience. However, these associations were in opposite directions. Trust was associated with a small decrease in mental distress over time and transcendent experience was associated with a small increase in mental distress over time. The results confirm the importance of meaning in life, trust, and transcendent experience as elements of mental health.