ER presented a largely positive and affirming portrayal of LGBTQ+ characters, most notably through Dr. Kerry Weaver's extensive storyline. Her journey of self-acceptance, loving relationships, and facing external prejudice was handled with empathy and depth, validating queer lives and love.

ER featured transsexual characters in storylines that addressed both medical needs and social challenges. While depicting external prejudice and tragic circumstances, the show's narrative generally fostered empathy among its medical staff and aimed to humanize trans individuals, framing obstacles as external forces rather than inherent flaws. The overall portrayal leaned towards respectful and understanding.

The show portrays Christianity with respect and nuance, often exploring characters' personal faith journeys and the role of religion in coping with suffering. Figures like Sister Carol exemplify compassion and dedication, while the narrative generally treats Christian beliefs as a source of comfort and moral guidance.

Islam is portrayed with sensitivity and respect, particularly when addressing the cultural and religious practices of Muslim patients and their families. The show navigates differences with dignity, aiming for an understanding and non-judgmental representation.

Judaism is depicted respectfully, primarily through patient stories and cultural practices. The narrative highlights the importance of family and tradition in times of crisis, demonstrating sensitivity to Jewish customs without negative stereotyping.