Background Minority stress has traditionally been explored at the individual level, particularly among LGBTQ+ populations. However, the experiences of couple-level minority stress in trans-inclusive relationships, where at least one partner is transgender, are underexplored. This study seeks to understand the unique stressors and coping mechanisms within these relationships, considering the compounded stress from multiple marginalized identities. Methods A qualitative approach was used, involving semi-structured interviews with 10 Italian trans-inclusive couples. Participants were invited to participate from November 2021 to July 2022. Data were analyzed through template analysis as a qualitative approach to thematic analysis, identifying stress levels and themes. The coding process was iterative, involving multiple rounds to refine themes and sub-themes. Results Ten themes were identified and organized into four levels of analysis: 1) Systemic level, encompassing perceived safety, social representation, and legal and social disparities; 2) Familial level, comprising experiences of discrimination, devaluation of relationship identity, and emotional impact; 3) Social interaction level, involving microaggressions and social exclusion; and 4) Intra-couple level, exploring shared stress and comparative couple-image. Discussion The findings highlight that trans-inclusive couples experience a complex interplay of stressors at multiple levels, which are influenced by both external perceptions and internal dynamics. Understanding these stressors is crucial for developing supportive interventions that address the unique needs of these couples. The study emphasizes the importance of considering intersectionality in minority stress research to capture the diverse experiences within trans-inclusive relationships.