The Ciénaga Grande de Santa Marta (CGSM) is the largest coastal lagoon in the Colombian Caribbean. Declared Biosphere Reserve and Ramsar Site, it is a strategic ecosystem for the conservation of global biodiversity. However, it is also considered an environmentally disturbed area due to natural and anthropogenic threats which increase pollution and affect the ecosystem’s environmental quality. With the purpose of having information that contributes to the assessment and management of environmental pollution of the CGSM, land-based sources pollutions of the lagoon complex were evaluated in the period between 1997 and 2006; pollutant loads carried by the Magdalena river and tributaries flowing down from the Sierra Nevada de Santa Marta were calculated as well using the methodology proposed by UNEP’s Caribbean Environment Programme and historical water quality monitoring data of the area. Loads were also calculated for domestic, microbiological and solid waste produced by the population of the study area. Results indicate that water resources are most affected by the pollution load from domestic, agricultural, and industrial waste which are carried by the tributaries and runoff. These sources induce organic pollution that reaches the CGSM in terms of solids, nitrogen, phosphorus, and fecal microorganisms, which generate risks to human health, and the aquatic flora and fauna. The identification of sources and pollutant loads serve as technical support to implement management measures that improve environmental conditions and to the life quality for residents in the CGSM.