Natural rubber has been successfully used in a marine environment for many years. However, most applications involve low dynamic loadings. Due to the emergence of marine energy recovery, wave and tidal energy converters are being developed. In some such devices, rubbers are subjected to severe cyclic loadings, very different from their previous use in air or water. Such rubbers must therefore be qualified for long-term use in sea water with high fatigue loading. This paper presents a study using a new fatigue machine that allows the fatigue behaviour of rubber in sea water to be compared to that in air. The results show that the benefit of non-relaxing conditions on fatigue lifetime of natural rubber can be significantly reduced when it is used in sea water, observed in particular for a ratio of minimum to maximum strain of R = 0.2. In order to understand this new result, the effects of both antioxidant and of minimum strain during the fatigue cycle were investigated. The effect of antioxidant was found to be the same in sea water and air, i.e. an increase of the stabiliser level leads to an increase in fatigue life, so It appears that antioxidant leaching is not the origin of the reduction of fatigue life in sea water. It was noted that this reduction of number of cycles to failure does not occur when natural rubber is used in sea water in fully relaxing cycles, suggesting that strain induced crystallisation, responsible for the beneficial effect of non-relaxing cycles on fatigue resistance, might be adversely influenced by sea-water at a ratio R of minimum to maximum strain equal to 0.2.