In Sub-Saharan Africa, health care facilities face critical challenges in water supply, sanitation, and hygiene services; health care waste management; and environmental cleanliness. With coverage below 50 percent, these deficiencies pose significant health risks to patients and health care workers, contributing to health care–associated infections. Meta-analyses and individual studies estimate rates of health care–associated infections in Sub-Saharan Africa at between 13 and 30 percent of hospital admissions, impacting patients, families, and health care providers. Rising antimicrobial resistance further exacerbates health outcomes and costs. In Eastern and Southern Africa, an estimated 3.1 million health care–associated infections in 2022 incurred over 320,000 excess deaths, costing at least US$6 billion, or 1.14 percent of combined gross domestic product in 2022. Investing in comprehensive water supply, sanitation, and hygiene and health care waste management can yield substantial benefits, with a benefit-cost ratio of 5.8 for all economic costs. Beyond preventing health care–associated infections, improved cleanliness and infrastructure are crucial for patient satisfaction, impacting future health care–seeking behavior and health care worker job satisfaction. Sub-Saharan African countries should prioritize infrastructure investment, budget allocation, staffing, and behavioral improvements to enhance the quality of health care and mitigate these pressing challenges.