Objective To explore the pregnancy-related stresses anticipated and experienced by women with phenylketonuria (PKU) and the coping strategies and supports utilised or anticipated to be beneficial during pregnancy. Methods Thematic analysis of interview data from eight women with PKU in a cross-sectional, qualitative study. Five of the participants had never had a pregnancy but were planning to in the future, two participants had children, and one participant was pregnant. Results The central concern regarding pregnancy was achieving and maintaining the essential low Phe levels, in the context of the devastating effects of high levels. The Transactional Model of Stress and Coping was utilised to understand the coping strategies and supports utilised or anticipated to be beneficial during pregnancy. Similarities and differences between the women who had experienced pregnancy, and those who were planning a pregnancy in the future were evident in key coping strategies, with knowledge seeking, positive reappraisal, and reassurance seeking reported. Support from health professionals and other mothers with PKU was key for all women. Psychological support was identified as a resource perceived to be beneficial to promote psychological well-being during pregnancy but not yet provided. Conclusion Pregnancy is associated with significant stresses for women with PKU. Clinical implications of the findings include provision of psychological support.