The series "Who Killed Sara?" features prominent LGBTQ+ characters, including Chema Lazcano and his partner Lorenzo, whose relationship and desire for a family are central to the plot. Marifer's lesbian identity and her relationship with Daniela are also depicted. While characters face external challenges like homophobia, the narrative explores these relationships with depth and complexity, affirming the worth of queer lives and love within its dramatic framework.

The series features a significant transsexual character, Marifer, whose identity is portrayed with dignity and complexity. Her journey and struggles are integrated into the overarching mystery, showcasing her agency and multifaceted personality rather than reducing her to a stereotype. The narrative treats her identity respectfully, framing her challenges as part of the dramatic plot rather than a condemnation of her trans experience.

The series "Who Killed Sara?" portrays a wealthy family unit riddled with corruption, abuse, and infidelity, consistently undermining traditional family structures and parental authority. It normalizes alternative relationships and behaviors, presenting a strong critique of conventional family norms.