Health conditions affecting women in the perinatal period still account for a major contribution to disease burden in Sub-Saharan Africa, yet there is a dearth of empirical research to understanding health professionals’ perspective on their experiences and how they care for perinatal women in depression. We used a qualitative exploratory descriptive approach through a face- to face-interview to explore the knowledge of 11 health professionals of Komfo Anokye Teaching Hospital, Kumasi- Ghana. Interviews were taped recorded and transcribed verbatim. The study adopted Haase’s modification of Colaizzi’s method for the analysis. Four main themes emerged: ineffective communication (Referral lapses among care providers, long waiting time, lack of confidentiality), workload (Inefficient staff to meet perinatal women’s need, no screening tools and time constraints), Reaction to patients symptoms (Identifying patient’s symptoms, assessment through patient’s centeredness and Education and counselling). Our results emerged that time constraints, stigmatization and lack of awareness delayed the care and management of perinatal depression among healthcare professionals in the hospital setting. There is the need to improve healthcare professionals’ knowledge on perinatal depression and it is imperative for the hospital administrators to invest in continuous training and professional development for healthcare professionals.