The objective of the current study was to determine seasonal changes in glucose, cholesterol, non-esterified fatty acids (NEFA), serum inorganic phosphorous (SIP), calcium, magnesium and iron concentrations in Nguni and crossbred cattle on the sweet and sour rangelands of the Eastern Cape Province of South Africa. Body weights, body condition scores (BCS) and serum concentrations of energy-related metabolites and mineral profiles were determined in late cool-dry, hot-dry, hot-wet, post-rainy and early cool-dry seasons in 100 cattle raised on communal rangelands from August 2007 to May 2008. Nguni cattle had lower (p<0.05) and higher (p<0.05) serum concentrations of glucose in the hot-wet and post-rainy seasons, respectively, compared to crossbreds in the same seasons. Serum cholesterol and NEFA concentrations in Nguni were lower (p<0.05) than in the crossbreds. Nguni and crossbred cattle had higher (p<0.05) serum NEFA concentrations on the sweet rangeland during the late cool-dry season than on sour rangeland. Nguni cattle had higher (p<0.05) SIP concentration in the hot-wet season than the crossbreds. Generally, both breeds had lowest SIP concentration during the hot-wet season on the sour rangeland. The lowest magnesium and highest iron concentrations were observed in the hot-wet and post-rainy seasons, respectively, compared to other seasons. Cattle on the sour rangeland had lower (p<0.05) iron concentrations than those on the sweet rangeland. It was concluded that Nguni cattle had lower cholesterol and NEFA, and higher SIP concentrations in the hot-wet season than crossbreds and energy deficits mostly occurred during the late cool-dry season on the sweet rangeland.