The source of emerging diseases and antimicrobial resistance is of increasing interest to epidemiologists. This paper looks at village chickens as such a source. In addition, infectious diseases constitute a major challenge to the growth and profitability of the rural poultry sector in Sub-Saharan Africa. A serological survey was conducted to estimate the apparent seroprevalence of selected chicken diseases in the Eastern Cape Province of South Africa alongside a sociological survey of poultry farmers and the remedies most commonly used to prevent diseases in their flocks. Sera collected from village chickens (n = 1007) in the province were screened for specific antibodies against Newcastle disease (ND), avian influenza (AI), avian infectious bronchitis (IB) and Mycoplasma gallisepticum (MG). The overall seroprevalence of ND, AI, IB and MG in the province was found to be 69.2 % (95 % CI 51.9−86.5%); 1.8 % (95 % CI 0.2−3.4%); 78.5 % (95 % CI 74.9−82%) and 55.8 % (95 % CI 41.3−70.3%) respectively with clustering found at the District level. Cross hemagglutination inhibition (HI) tests indicated that the chickens were exposed to the ND vaccine. AI ELISA-positive samples were tested using HIs against the H5, H6 and H7-subtypes, but only H6-specific antibodies were detected. Avian influenza strains shared the common ancestor responsible for the 2002 chicken outbreak in KwaZulu-Natal Province. The majority of chicken farmers were females and pensioners (69 % and 66.1 % respectively) and had a primary school education (47.1 %). Traditional remedies were commonly used by farmers (47.15 %) and among the remedies, Aloe plant (Aloe ferox Mill.) or ikhala (Xhosa) was the most commonly used product (28.23 %) for preventing and reducing mortalities among village chickens. The findings stress the importance of village chickens as a substitute for social welfare and highlight the exposure of village chickens to important chicken pathogens. The economic impact of these pathogens on the development of this sub-sector needs further investigation. Village chickens are a potential source of virulent Newcastle disease virus (NDV) because of the lack of vaccination and biosecurity. They may serve as amplification hosts which increases the probability that virulent NDV could spill over into commercial poultry flocks due to large amounts of circulating virus. The zoonotic threat of circulating H6N2 viruses raise concern due to their mutation and reassortment among chickens and a potential movement of infected birds within the province. Finally, the use of antibiotics by untrained chicken farmers constitute another major concern as it could serve as a source of antimicrobial resistance (AMR).