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The present study was conducted to investigate the risk factors for post-mortem findings and causes of sow mortality. A post-mortem examination and microbiological investigation were conducted on 123 sows from a breeding herd with 15,000 dams. The mortality of spontaneous death in sows occurred mostly in the peripartum period (53%; p < 0.05). The spontaneous deaths were associated with heart failures, hemorrhagic and perforating gastric ulcers, and liver torsion, while in the euthanized sows, the post-mortem findings were associated with locomotor disorders. A higher body condition score (BCS ≥ 3.5) increased (p < 0.05) heart failure on the post-mortem examination. The excessive use of manual obstetric interventions increased sow deaths resulting from cervix/uterus ruptures and increased the odds of death (p < 0.05) due to metritis. Sow mortality had a multifactorial etiology. Infections were polymicrobial. The main microbial agents identified from a septic lesion in locomotor, genitourinary, and respiratory systems were Trueperella pyogenes, Escherichia coli, and Actinobacillus pleuropneumoniae, respectively. In conclusion, sow mortality involved multiple risk factors and several bacterial agents. These results indicate that better management practices can reduce sow mortality in swine production and increase sow welfare.