The European cuttlefish (Sepia officinalis) is often kept in public aquaria, is becoming more common in aquaculture, and is also the most frequently used cephalopod in European research. Since 1st January 2013, all cephalopods (Mollusca) have been protected under UK/EU law (A(SP)A 1986, European Directive 2010/63/EU), following Australia, Canada and New Zealand. Presently, unlike other organisms used in research, there is no detailed specific guidance available from UK/EU legislators on best practices for keeping cuttlefish. In captivity, juveniles can easily become damaged by impacting with tank walls when startled. These injuries rarely heal and can have a major impact on growth and survival. Six experiments were performed, using juvenile and adult cuttlefish, in which exhibition of thigmotaxis in different environments, responses to simulated husbandry in different scenarios, and responses to typical and novel forms of enrichment (e.g. photographs of substrates) and refuges was investigated. Refuge use was also investigated, including response to husbandry when different refuges were provided. In addition to thigmotaxis, the frequency of negative behaviours (such as those likely indicating stress or preceding damaging behaviours) was recorded. The results suggest that certain environments, clothing/equipment and refuges/enrichment can significantly reduce the frequency of negative behaviours. It was also found fake seaweed and photographs of substrates placed in tanks may be used by cuttlefish with the benefit of preventing localised pollution. We conclude by providing an evidence-based guide to improving husbandry practices, which could improve the lives of captive cuttlefish.