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Viral respiratory infections (VRIs) remain a leading cause of global morbidity and mortality. In Djibouti, diagnostic capacity for respiratory viruses is extremely limited, and little is known about the epidemiology of VRIs in the country. To address this gap, we conducted a prospective study aimed at monitoring and describing the epidemiological and virological features of VRIs over a two-year period in Djibouti. The study was carried out between January 2023 and December 2024 in seven healthcare centers. Nasopharyngeal and/or oropharyngeal swabs were collected from consenting patients presenting with influenza-like illness (ILI) or acute respiratory infections (ARI). VRIs were diagnosed using a multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assay targeting 16 respiratory viruses. Among the 647 samples tested, at least one respiratory virus was detected in 133 (20.6%). Influenza (6.6%), rhinovirus (5.9%), and SARS-CoV-2 (3.4%) were the most frequently detected pathogens. Adult aged 26-50 years (40.8%) were the most affected, followed by those aged 15-25 years (30.4%). None of the respiratory viruses displayed a clear seasonal pattern. These findings demonstrate the co-circulation of multiple respiratory viruses among ILI/ARI patients in Djibouti and provide the first baseline data to inform national surveillance strategies. The results underscore the need to strengthen routine laboratory-based surveillance, enhance diagnostic capacity, and integrate molecular monitoring into national public health policies for better preparedness against emerging respiratory threats.