Introduction: Post-partum depression (PPD), identifiable within a specific period starting during pregnancy or within the first four weeks after birth, presents an opportunity for early detection and diagnosis at the primary healthcare level. This study evaluates the awareness of PPD and its influencing factors among healthcare professionals in a city in Saudi Arabia. Methods: Conducted as a cross-sectional survey among primary healthcare workers, the study included 110 participants, determined with a 95% confidence level and a 5% error margin. Utilizing a two-part validated questionnaire, the research gathered socio-demographic data and evaluated knowledge on PPD, covering symptoms, identification, risk factors, diagnosis, and treatment. Results: Among the 110 health workers surveyed, two-thirds were female, and half were between the ages of 21-34. The majority were general practitioners (53.6%), followed by registrars (15.5%) and consultants (18.2%). Around 44% occasionally screened for PPD, whereas 44.5% did so rarely or never. Knowledge scores on PPD varied from 11 to 41, with an average of 30.6±6.6. While 58.2% exhibited a high understanding of PPD, 9.1% showed low awareness. Significant factors affecting PPD knowledge were medical qualifications and job titles, whereas age and gender were not significantly related. Conclusions: Knowledge about PPD among healthcare workers in primary care settings was generally satisfactory but showed gaps in certain areas, such as screening, diagnosis, and understanding of complications. Although there was a significant awareness of the symptoms and treatment of PPD, knowledge on screening and diagnosis was lacking.