Aims: Peste des petits Ruminants (PPR) is a major viral disease that poses a challenge to small ruminant farming. Its natural occurrence has been complicated by secondary bacterial infection which has led to an increase in morbidity and mortality rates. This study reports the management outcome of natural PPR-infected goats using two types of antibiotics in Nsukka metropolis of Enugu State Nigeria. Methodology: Goats (N=24) were confirmed to be suffering from PPR based on clinical signs and using polymerase chain reaction (PCR). The animals were divided into two groups. Group A was treated with 20% oxytetracycline (N= 10) and group B with procaine penicillin and streptomycin combination (penstrept) (N= 14) injection. Clinical signs, recovery and survivability, temperature, haematology [Packed cell volume (PCV); haemoglobin concentration (Hbconc); red blood cell (RBC) and white blood cell (WBC) counts] and some serum biochemical profiles [alanine aminotransferase (ALT); aspartate transaminase (AST); total protein (TP); Albumin; urea; creatinine; potassium and sodium] were used to assess the efficacy of the antibiotics using standard techniques. Results: The mean temperature, RBC, WBC and urea values of the PPR-infected goats were above their reference ranges, mean albumin values were below the reference range while mean Hbconc, PCV, AST, ALT, TP and creatinine values were within their reference range before the commencement of treatment. Following treatment, clinical signs cleared in 20% and 35.7% of the goats treated with oxytetracycline and penstrep respectively. Death was recorded in 20% and 15% of goats treated with oxytetracycline and penstrep respectively before the end of treatment. Penstrep-treated group showed improvement in their haematological profile. Conclusion: Based on our findings, the use of penstrep in the management of PPR-infected goats gave a better result.